Generating anti-infective design spaces for selecting drug candidates

ABSTRACT

In one aspect, a method includes generating a design space for a peptide for an application. The generating includes identifying sequences for the peptide, and updating the sequences by determining, for each of the sequences, a respective set of activities pertaining to the application. The updating produces updated sequences each having updated respective activities. The method includes generating, based on the updated sequences, a solution space within the design space. The solution space includes a target subset of the updated sequences. The method includes performing, using a machine learning model to process the solution space, trials to identify a candidate drug compound that represents a sequence having a level of activity that exceeds a threshold level, and transmitting information describing the candidate drug compound to a computing device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This applications claims the benefit of U.S. Provisional ApplicationSer. No. 63/117,068, filed Nov. 23, 2020 titled “GeneratingAnti-Infective Design Spaces for Selecting Drug Candidates”. Theprovisional application is incorporated by reference herein as ifreproduced in full below.

TECHNICAL FIELD

This disclosure relates generally to drug discovery. More specifically,this disclosure relates to generating anti-infective design spaces forselecting drug candidates.

BACKGROUND

Therapeutics may refer to a branch of medicine concerned with thetreatment of disease and the action of remedial agents (e.g., drugs).Therapeutics includes, but is not limited to, the field of ethicalpharmaceuticals. Entities in the therapeutics industry may discover,develop, produce, and market drugs for use as medications to beadministered or self-administered to patients. Goals of administering orself-administering the drugs may include curing the patient of adisease, causing an active disease to enter a state of remission,vaccinating the patient by stimulating the immune system to betterprotect against the disease, and/or alleviating, mitigating orameliorating a symptom. Existing drug discoveries may be based on anycombination of human design, high-throughput screening, syntheticproducts and natural substances.

SUMMARY

In one aspect, a method includes generating a design space for a protein(e.g., peptide) for an application (e.g., drug application, industrialapplication, veterinary application, environmental recovery application(e.g., oil spill, plastics in waterways and oceans), etc.). Theapplication may refer to a chemical application (e.g., drug) for whichthe protein is designed. The generating includes identifying sequencesfor the peptide, and updating the sequences by determining, for each ofthe sequences, a respective set of activities pertaining to theapplication. The updating produces updated sequences each having updatedrespective activities. The method includes generating, based on theupdated sequences, a solution space within the design space. Thesolution space includes a target subset of the updated sequences. Themethod includes performing, using a machine learning model to processthe solution space, trials to identify a candidate drug compound thatrepresents a sequence having a level of activity that exceeds athreshold level, and transmitting information describing the candidatedrug compound to a computing device.

In another aspect, a system may include a memory device storinginstructions and a processing device communicatively coupled to thememory device. The processing device may execute the instructions toperform one or more operations of any method disclosed herein.

In another aspect, a tangible, non-transitory computer-readable mediummay store instructions and a processing device may execute theinstructions to perform one or more operations of any method disclosedherein.

Other technical features may be readily apparent to one skilled in theart from the following figures, descriptions, and claims.

Before undertaking the DETAILED DESCRIPTION below, it may beadvantageous to set forth definitions of certain words and phrases usedthroughout this patent document. The term “couple” and its derivativesrefer to any direct or indirect communication between two or moreelements, independent of whether those elements are in physical contactwith one another. The terms “transmit,” “receive,” and “communicate,” aswell as derivatives thereof, encompass both direct and indirectcommunication. The terms “transmit,” “receive,” and “communicate,” aswell as derivatives thereof, encompass both communication with remotesystems and communication within a system, including reading and writingto different portions of a memory device. The terms “include” and“comprise,” as well as derivatives thereof, mean inclusion withoutlimitation. The term “or” is inclusive, meaning and/or. The phrase“associated with,” as well as derivatives thereof, means to include, beincluded within, interconnect with, contain, be contained within,connect to or with, couple to or with, be communicable with, cooperatewith, interleave, juxtapose, be proximate to, be bound to or with, have,have a property of, have a relationship to or with, or the like. Theterm “translate” may refer to any operation performed wherein data isinput in one format, representation, language (computer,purpose-specific, such as drug design or integrated circuit design),structure, appearance or other written, oral or representableinstantiation and data is output in a different format, representation,language (computer, purpose-specific, such as drug design or integratedcircuit design), structure, appearance or other written, oral orrepresentable instantiation, wherein the data output has a similar oridentical meaning, semantically or otherwise, to the data input.Translation as a process includes but is not limited to substitution(including macro substitution), encryption, hashing, encoding, decodingor other mathematical or other operations performed on the input data.The same means of translation performed on the same input data willconsistently yield the same output data, while a different means oftranslation performed on the same input data may yield different outputdata which nevertheless preserves all or part of the meaning or functionof the input data, for a given purpose. Notwithstanding the foregoing,in a mathematically degenerate case, a translation can output dataidentical to the input data. The term “controller” means any device,system or part thereof that controls at least one operation. Such acontroller may be implemented in hardware or a combination of hardwareand software and/or firmware. The functionality associated with anyparticular controller may be centralized or distributed, whether locallyor remotely. The phrase “at least one of,” when used with a list ofitems, means that different combinations of one or more of the listeditems may be used, and only one item in the list may be needed. Forexample, “at least one of: A, B, and C” includes any of the followingcombinations: A, B, C, A and B, A and C, B and C, and A and B and C.

Moreover, various functions described below can be implemented orsupported by one or more computer programs, each of which is formed fromcomputer readable program code and embodied in a computer readablestorage medium. The terms “application” and “program” refer to one ormore computer programs, software components, sets of instructions,procedures, functions, objects, classes, instances, related data, or aportion thereof adapted for implementation in a suitable computerreadable program code. The phrase “computer readable program code”includes any type of computer code, including source code, object code,and executable code. The phrase “computer readable storage medium”includes any type of medium capable of being accessed by a computer,such as read only memory (ROM), random access memory (RAM), a hard diskdrive, a compact disc (CD), a digital video disc (DVD), solid statedrive (SSD), or any other type of memory. A “non-transitory” computerreadable storage medium excludes wired, wireless, optical, or othercommunication links that transport transitory electrical or othersignals. A non-transitory computer readable storage medium includesmedia where data can be permanently stored and media where data can bestored and later overwritten, such as a rewritable optical disc or anerasable memory device.

The terms “candidate drugs” and “candidate drug compounds” may be usedinterchangeably herein.

Definitions for other certain words and phrases are provided throughoutthis patent document. Those of ordinary skill in the art shouldunderstand that in many if not most instances, such definitions apply toprior as well as future uses of such defined words and phrases.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of this disclosure and its advantages,reference is now made to the following description, taken in conjunctionwith the accompanying drawings, in which:

FIG. 1A illustrates a high-level component diagram of an illustrativesystem architecture according to certain embodiments of this disclosure;

FIG. 1B illustrates an architecture of the artificial intelligenceengine according to certain embodiments of this disclosure;

FIG. 1C illustrates first components of an architecture of the creatormodule according to certain embodiments of this disclosure;

FIG. 1D illustrates second components of the architecture of the creatormodule according to certain embodiments of this disclosure;

FIG. 1E illustrates an architecture of a variational autoencoderaccording to certain embodiments of this disclosure;

FIG. 1F illustrates an architecture of a generative adversarial networkused to generate candidate drugs according to certain embodiments ofthis disclosure;

FIG. 1G illustrates types of encodings to represent certain types ofdrug information according to certain embodiments of this disclosure;

FIG. 1H illustrates an example of concatenating numerous encodings intoa candidate drug according to certain embodiments of this disclosure;

FIG. 1I illustrates an example of using a variational autoencoder togenerate a latent representation of a candidate drug according tocertain embodiments of this disclosure;

FIG. 2 illustrates a data structure storing a biological contextrepresentation according to certain embodiments of this disclosure;

FIGS. 3A-3B illustrate a high-level flow diagram according to certainembodiments of this disclosure;

FIG. 4 illustrates example operations of a method for generating andclassifying a candidate drug compound according to certain embodimentsof this disclosure;

FIGS. 5A-5D provide illustrations of generating a first data structureincluding a biological context representation of a plurality of drugcompounds according to certain embodiments of this disclosure;

FIG. 6 illustrates example operations of a method for translating thefirst data structure of FIGS. 5A-5D into a second data structure havinga second format according to certain embodiments of this disclosure;

FIG. 7 provide illustrations of translating the first data structure ofFIGS. 5A-5D into the second data structure having the second formataccording to certain embodiments of this disclosure;

FIG. 8A-8C provide illustrations of views of a selected candidate drugcompound according to certain embodiments of this disclosure;

FIG. 9 illustrates example operations of a method for presenting a viewincluding a selected candidate drug compound according to certainembodiments of this disclosure;

FIG. 10A illustrates example operations of a method for using causalinference during the generation of candidate drug compounds according tocertain embodiments of this disclosure;

FIG. 10B illustrates another example of operations of a method for usingcausal inference during the generation of candidate drug compoundsaccording to certain embodiments of this disclosure;

FIG. 11 illustrates example operations of a method for using severalmachine learning models in an artificial intelligence enginearchitecture to generate peptides according to certain embodiments ofthis disclosure;

FIG. 12 illustrates example operations of a method for performing abenchmark analysis according to certain embodiments of this disclosure;

FIG. 13 illustrates example operations of a method for slicing a latentrepresentation based on a shape of the latent representation accordingto certain embodiments of this disclosure;

FIG. 14 illustrates a high-level flow diagram for a therapeutics toolimplementing business intelligence according to certain embodiments ofthis disclosure;

FIG. 15 illustrates an example user interface for using query parametersto generate a solution space that includes protein sequences accordingto certain embodiments of this disclosure;

FIG. 16 illustrates an example user interface for tracking informationpertaining to trials according to certain embodiments of thisdisclosure;

FIG. 17 illustrates an example user interface for presenting performancemetrics of machine learning models that perform trials according tocertain embodiments of this disclosure;

FIG. 18 illustrates an example user interface for a candidate dashboardscreen according to certain embodiments of this disclosure;

FIG. 19 illustrates example operations of a method for generating adesign space for a peptide for an application according to certainembodiments of this disclosure;

FIG. 20 illustrates example operations of a method for comparingperformance metrics of machine learning models according to certainembodiments of this disclosure;

FIG. 21 illustrates example operations of a method for presenting adesign space and a solution space within a graphical user interface of atherapeutics tool according to certain embodiments of this disclosure;

FIG. 22 illustrates example operations of a method for receiving andpresenting of one or more results of performing a selected trial using amachine learning model according to certain embodiments of thisdisclosure;

FIG. 23 illustrates example operations of a method for using a businessintelligence screen to select a desired target product profile forsequences according to certain embodiments of this disclosure; and

FIG. 24 illustrates an example computer system according to certainembodiments of this disclosure.

DETAILED DESCRIPTION

Conventional drug discoveries based on human design, high-throughputscreening, or natural substances may be inefficient, riven with noise,limited in application, not efficacious, dangerous or poisonous, or notdefensible. Further, in some instances, there are instances of certaindiseases (e.g., instances of prosthetic joint infections) that do nothave a corresponding existing therapeutic to treat the certain diseasesor which provide temporary results against which the disease isrefractory. One reason for the lack of an existing therapeutic may bethe conventional drug discovery techniques are incapable of discoveringthe therapeutic needed to treat the certain diseases. By “treat,” wemean that the disease at hand is cured inter alia, that it is notrefractory to treatment. The amount of knowledge, data, assumptions, andqueries used to discover a therapeutic to treat the certain disease maybe unattainable, overwhelming, or inefficiently determined, such thatconventional drug discovery techniques cannot overcome these obstacles.Improvement is desired in the field of therapeutics.

Further, conventional techniques for searching for candidate drugs uselimited design spaces. For example, some conventional techniques focuson a fact about drugs, where such facts constrain the design space thatis searched. The design space may refer to parameterization of limitsand constraints in a drug space where candidate drug compounds may bedesigned. A design space may also refer to a multidimensionalcombination and interaction of input variables (e.g., materialattributes) and process parameters that have been demonstrated toprovide assurance of quality. An example of such a fact may include acertain biomedical activity known to be linked to an alpha-helixphysical structure of a peptide, where conventional techniques maysearch for other activities that may result from a peptide having thealpha-helix physical structure. Such a limited design space may limitthe results obtained. Thus, it is desirable to enlarge the design spaceto account for other information such as drug sequence information, drugactivity information, drug semantic information, drug chemicalinformation, drug physical information, and so forth. However, enlargingthe design space may increase the complexity of searching the designspace.

Accordingly, aspects of the present disclosure generally relate to anartificial intelligence engine for generating candidate drugs. By usingvarious encoding types that enable performing searches in the designspace in an efficient manner, the artificial intelligence engine (AI)may enlarge the design space to include the combination of druginformation (e.g., structural, physical, semantic, activity, sequence,chemical, attributes expressed in solubility data, properties expressedin solubility data, related structures, related drugs, chemicalsynthesis, biological synthesis, intellectual property data, clinicaldata, market data, etc.). The architecture of the AI engine may includevarious computational techniques that reduce the computationalcomplexity of using a large design space, thereby saving computingresources (e.g., reducing computing time, reducing processing resources,reducing memory resources, etc.). At the same time, the disclosedarchitecture may generate superior candidate drugs that includedesirable features (e.g., structure, semantics, activity, sequence,clinical outcomes, etc.) found in the larger design space as compared toconventional techniques using the smaller design space.

The artificial intelligence (AI) engine may use a combination ofrational algorithmic discovery and machine learning models (e.g.,generative deep learning methods) to produce enhanced therapeutics thatmay treat any suitable target disease or medical condition. The AIengine may discover, translate, design, generate, create, develop,formulate, classify, or test candidate drug compounds that exhibitdesired activity (e.g., antimicrobial, immunomodulatory, cytotoxic,neuromodulatory, etc.) in design spaces for target diseases or medicalconditions. Such candidate drug compounds that exhibit desired activityin a design space may effectively treat the disease or medical conditionassociated with that design space. In some embodiments, a selectedcandidate drug compound that effectively treats the disease or medicalcondition may be formulated into an actual drug for administration andmay be tested in a lab or at a clinical stage.

In general, the disclosed embodiments may enable rationally discovery ofdrug compounds for a larger design space at a larger scale, higheraccuracy, or higher efficiency than conventional techniques. The AIengine may use various machine learning models to discover, translate,design, generate, create, develop, formulate, classify, or testcandidate drug compounds. Each of the various machine learning modelsmay perform certain specific operations. The types of machine learningmodels may include various neural networks that perform deep learning,computational biology, or algorithmic discovery. Examples of such neuralnetworks may include generative adversarial networks, recurrent neuralnetworks, convolutional neural networks, fully connected neuralnetworks, etc., as described further below; and such networks may alsoadditionally employ methods of or incorporating causal inference,including counterfactuals, in the process of discovery.

In some embodiments, a biological context representation of a set ofdrug compounds may be generated. The biological context representationmay be a continuous representation of a biological setting that isupdated as knowledge is acquired or data is updated. The biologicalcontext representation may be stored in a first data structure having aformat (e.g., a knowledge graph) that includes both various nodespertaining to health artifacts and various relationships connecting thenodes. The nodes and relationships may form logical structures havingsubjects and predicates. For example, one logical structure between twonodes having a relation may be “Genes are associated with Diseases”where “Genes” and “Diseases” are the subjects of the logical structureand “are associated with” is the relation. In such a way, the knowledgegraph may encompass actual knowledge, rather than simply statisticalinferences, pertaining to a biological setting.

The information in the knowledge graph may be continuously orperiodically updated and the information may be received from varioussources curated by the AI engine. The knowledge in the biologicalcontext representation goes well beyond “dumb” data that just includesquantities of a value because the knowledge represents the relationshipsbetween or among numerous different types of data, as well as any or allof direct, indirect, causal, counterfactual or inferred relationships.In some embodiments, the biological context representation may not bestored, and instead, based on the stream of knowledge included in thebiological context representation, may be streamed from data sourcesinto the AI engine that generates the machine learning models.

The biological context representation may be used to generate candidatedrug compounds by translating the first data format to a second datastructure having a second format (e.g., a vector). The second format maybe more computationally efficient or suitable for generating candidatedrug compounds that include sequences of ingredients that providedesired activity in a design space. “Ingredients” as used herein mayrefer, without limitation, to substances, compounds, elements,activities (such as the application or removal of electrical charge or amagnetic field for a specific maximum, minimum or discrete amount oftime), and mixtures. Further, the second format may enable generatingviews of the levels of activity provided by the sequence of ingredientsin a certain design space, as described further below.

At a high level, the AI engine may include at least one machine learningmodel that is trained to use causal inference to generate candidate drugcompounds. One of the challenges with discovering new therapeutics mayinclude determining whether certain ingredients may be causal agentswith respect to certain activity in a design space. The sheer number ofpossible sequences of ingredients may be extraordinarily large due tomathematical combinatorics, such that identifying a cause and effectrelationship between ingredients and activity may be impossible or, atbest, extremely unlikely, to identify without the disclosed embodiments.(For example, in public-key encryption, it is theoretically possible todiscover and unlock a private key, but doing this would presentlyrequire all the computing power in the world to work longer than the ageof the universe: this is an example of what is mathematically possible,but impossible within human time frames and computing power. Identifyinga cause-and-effect relationship between ingredients and activity, whilea different problem, may be similarly mathematically possible, butimpossible within human time frames and computer power.) Based onadvances in computing hardware (e.g., graphic processing unit processingcores) and the AI techniques using causal inference described herein,the disclosed embodiments may enable the efficient solving of the taskof generating candidate drug compounds at scale.

Causal inference may refer to a process, based on conditions of anoccurrence of an effect, of drawing a conclusion about a causalconnection. Causal inference may analyze a response of an effectvariable when a cause is changed. Causation may be defined thusly: avariable Xis a cause of Y if Y “listens” to X and determines itsresponse based on what it “hears.” The process of causal inference inthe field of AI may be particularly beneficial for generating andtesting candidate drug compounds for certain diseases or medicalconditions because of the use of what are termed counterfactuals. Acounterfactual posits and examines conditions contrary to what hasactually occurred in reality. For example, if someone takes aspirin fora headache, the headache may go away. The counterfactual asks what wouldhave happened if the person had not taken aspirin, i.e., would theheadache still have gone away, or would it have remained or even gottenworse? Accordingly, counterfactuals may refer to calculating alternativescenarios based on past actions, occurrences, results, regressions,regression analyses, correlations, or some combination thereof. Acounterfactual may enable determining whether a response should stay thesame or instead change if something in a sequence does not occur. Forexample, one counterfactual may include asking: “Would a certain levelof activity be the same if a certain ingredient is not included in asequence of a candidate drug compound?”

By simulating numerous alternative scenarios to further optimize andhone the accuracy of a sequence of ingredients in the candidate drugcompounds, such techniques may enable reducing the number of viablecandidate drug compounds. As a result, the embodiments may providetechnical benefits, such as reducing resources consumed (e.g., time,processing, memory, network bandwidth) by reducing a number of candidatedrug compounds that may be considered for classification as a selectedcandidate drug compound by another machine learning model.

In some embodiments, one application for the AI engine to design,discover, develop, formulate, create, or test candidate drug compoundsmay pertain to peptide therapeutics. A peptide may refer to a compoundconsisting of two or more amino acids linked in a chain. Examplepeptides may include dipeptides, tripeptides, tetrapeptides, etc. Apolypeptide may refer to a long, continuous, and unbranched peptidechain. A cyclic peptide may refer to a polypeptide which contains acircular sequence of bonded amino acids. A modified peptide may refer toa synthesized peptide that undergoes a modification to a side chain,C-terminus, or N-terminus. Peptides may be simple to manufacture atdiscovery scale, include drug-like characteristics of small molecules,include safety and high specificity of biologics, or provide greateradministration flexibility than some other biologics.

The disclosed techniques provide numerous benefits over conventionaltechniques for designing, developing, or testing candidate drugcompounds. For example, the AI engine may efficiently use a biologicalcontext representation of a set of drug compounds and one or moremachine learning models to generate a set of candidate drug compoundsand classify one of the set of candidate drug compounds as a selectedcandidate drug compound. Some embodiments may use causal inference toremove one or more potential candidate drug compounds fromclassification, thereby reducing the computational complexity andprocessing burden of classifying a selected candidate drug compound.

In addition, benchmark analysis may be performed for each type ofmachine learning model that generates candidate drugs. The benchmarkanalysis may score various parameters of the machine learning modelsthat generate the candidate drugs. The various parameters may refer tocandidate drug novelty, candidate drug uniqueness, candidate drugsimilarity, candidate drug validity, etc. The scores may be used torecursively tune the machine learning models over time to cause one ormore of the parameters to increase for the machine learning models. Insome embodiments, some of the machine learning models may vary in theireffectiveness as it pertains to some of the parameters. In addition, togenerate subsequent candidate drug candidates, the benchmark analysismay score the candidate drug candidates generated by the machinelearning models, rank the machine learning models that generate thehighest scoring candidate drug candidates, or select the machinelearning models producing the highest scoring candidate drug candidates.

Also, certain markets (e.g., anti-infective, animal, industrial, etc.)may prefer, based on a type of data those markets generate, to usecertain machine learning models that generate high scores for a subsetof parameters. Accordingly, in some embodiments, the subset of machinelearning models that generate the high scores for the subset ofparameters may be combined into a package and transmitted to a thirdparty. That is, some embodiments enable custom tailoring of machinelearning model packages for particular needs of third parties based ontheir data.

Further, additional benefits of the embodiments disclosed herein mayinclude using the AI engine to produce algorithmically designed drugcompounds that have been validated in vivo and in vitro and that provide(i) a broad-spectrum activity against greater than, e.g., 900 multi-drugresistant bacteria, (ii) at least, e.g., a 2-to-10 times improvement inexposure time required to generate a drug resistance profile, (iii)effectiveness across, e.g., four key animal infection models (bothGram-positive and Gram-negative bacteria), or (iv) effectivenessagainst, e.g., biofilms.

It should be noted that the embodiments disclosed herein may not onlyapply to the anti-infective market (e.g., for prosthetic jointinfections, urinary tract infections, intra-abdominal or peritonealinfections, otitis media, cardiac infections, respiratory infectionsincluding but not limited to sequelae from diseases such as cysticfibrosis, neurological infections (e.g., meningitis), dental infections(including periodontal), other organ infections, digestive andintestinal infections (e.g., C. difficile), other physiological systeminfections, wound and soft tissue infections (e.g., cellulitis), etc.),but to numerous other suitable markets or industries. For example, theembodiments may be used in the animal health/veterinary industry, forexample, to treat certain animal diseases (e.g., bovine mastitis). Also,the embodiments may be used for industrial applications, such asanti-biofouling, or generating optimized control action sequences formachinery. The embodiments may also benefit a market for new therapeuticindications, such as those for eczema, inflammatory bowel disease,Crohn's Disease, rheumatoid arthritis, asthma, auto-immune diseases anddisease processes in general, inflammatory disease progressions orprocesses, or oncology treatments and palliatives. The video gameindustry may also benefit from the disclosed techniques to improve theAI used for generating sequences of decisions that non-player characters(NPC) make during gameplay. For example, the knowledge graph may includemultiple states of: player characters, non-player characters, levels,settings, actions, results of the actions, and so forth, and one or moremachine learning models may use the techniques described herein togenerate optimized sequences of decisions for NPCs to make duringgameplay when the states are encountered. The integrated circuit/chipindustry may also benefit from the disclosed techniques to improve themask works generation and routing processes used for generating the mostefficient, highest performance, lowest power, lowest heat generatingsystems on a chip or solid state devices. For example, the knowledgegraph may include configurations of mask works and routings of systemson chips or solid state drives, as well as their associated properties(e.g., efficiency, performance, power consumption, operatingtemperature, etc.). The disclosed techniques may generate one or moremachine learning models trained using the knowledge graph to generateoptimized mask works or routings to achieve desired properties.Accordingly, it should be understood that the disclosed embodiments maybenefit any market or industry associated with a sequence (e.g., items,objects, decisions, actions, ingredients, etc.) that can be optimized.

FIGS. 1A through 14, discussed below, and the various embodiments usedto describe the principles of this disclosure are by way of illustrationonly and should not be construed in any way to limit the scope of thedisclosure.

FIG. 1A illustrates a high-level component diagram of an illustrativesystem architecture 100 according to certain embodiments of thisdisclosure. In some embodiments, the system architecture 100 may includea computing device 102 communicatively coupled to a computing system116. The computing system 116 may be a real-time software platform,include privacy software or protocols, or include security software orprotocols. Each of the computing device 102 and components included inthe computing system 116 may include one or more processing devices,memory devices, or network interface cards. The network interface cardsmay enable communication via a wireless protocol for transmitting dataover short distances, such as Bluetooth, ZigBee, NFC, etc. Additionally,the network interface cards may enable communicating data via a wiredprotocol over short or long distances, and in one example, the computingdevice 102 and the computing system 116 may communicate with a network112. Network 112 may be a public network (e.g., connected to theInternet via wired (Ethernet) or wireless (WiFi)), a private network(e.g., a local area network (LAN) or wide area network (WAN)), or acombination thereof. In some embodiments, network 112 may also comprisea node or nodes on the Internet of Things (IoT).

The computing device 102 may be any suitable computing device, such as alaptop, tablet, smartphone, or computer. The computing device 102 mayinclude a display capable of presenting a user interface of anapplication 118. The application 118 may be implemented in computerinstructions stored on the one or more memory devices of the computingdevice 102 and executable by the one or more processing devices of thecomputing device 102. The application 118 may present various screens toa user that present various views (e.g., topographical heatmaps)including measures, gradients, or levels of certain types of activityand optimized sequences of selected candidate drug compounds,information pertaining to the selected candidate drug compounds or othercandidate drug compounds, options to modify the sequence of ingredientsin the selected candidate drug compound, and so forth, as described inmore detail below. The computing device 102 may also includeinstructions stored on the one or more memory devices that, whenexecuted by the one or more processing devices of the computing device102, perform operations of any of the methods described herein.

In some embodiments, the computing system 116 may include one or moreservers 128 that form a distributed computing system, which may includea cloud computing system. The servers 128 may be a rackmount server, arouter, a personal computer, a portable digital assistant, a mobilephone, a laptop computer, a tablet computer, a camera, a video camera, anetbook, a desktop computer, a media center, any other device capable offunctioning as a server, or any combination of the above. Each of theservers 128 may include one or more processing devices, memory devices,data storage, or network interface cards. The servers 128 may be incommunication with one another via any suitable communication protocol.The servers 128 may execute an artificial intelligence (AI) engine 140that uses one or more machine learning models 132 to perform at leastone of the embodiments disclosed herein. The computing system 128 mayalso include a database 150 that stores data, knowledge, and datastructures used to perform various embodiments. For example, thedatabase 150 may store a knowledge graph containing the biologicalcontext representation described further below. Further, the database150 may store the structures of generated candidate drug compounds, thestructures of selected candidate drug compounds, and informationpertaining to the selected candidate drug compounds (e.g., activity forcertain types of ingredients, sequences of ingredients, test results,correlations, semantic information, structural information, physicalinformation, chemical information, etc.). Although depicted separatelyfrom the server 128, in some embodiments, the database 150 may be hostedon one or more of the servers 128.

In some embodiments the computing system 116 may include a trainingengine 130 capable of generating one or more machine learning models132. Although depicted separately from the AI engine 140, the trainingengine 130 may, in some embodiments, be included in the AI engine 140executing on the server 128. In some embodiments, the AI engine 140 mayuse the training engine 130 to generate the machine learning models 132trained to perform inferencing operations. The machine learning models132 may be trained to discover, translate, design, generate, create,develop, classify, or test candidate drug compounds, among other things.The one or more machine learning models 132 may be generated by thetraining engine 130 and may be implemented in computer instructionsexecutable by one or more processing devices of the training engine 130or the servers 128. To generate the one or more machine learning models132, the training engine 130 may train the one or more machine learningmodels 132. The one or more machine learning models 132 may be used byany of the modules in the AI engine 140 architecture depicted in FIG. 2.

The training engine 130 may be a rackmount server, a router, a personalcomputer, a portable digital assistant, a smartphone, a laptop computer,a tablet computer, a netbook, a desktop computer, an Internet of Things(IoT) device, any other desired computing device, or any combination ofthe above. The training engine 130 may be cloud-based, be a real-timesoftware platform, include privacy software or protocols, or includesecurity software or protocols.

To generate the one or more machine learning models 132, the trainingengine 130 may train the one or more machine learning models 132. Thetraining engine 130 may use a base data set of biological contextrepresentation (e.g., physical properties data, peptide activity data,microbe data, antimicrobial data, anti-neurodegenerative compound data,pro-neuroplasticity compound data, clinical outcome data, etc.) for aset of drug compounds. For example, the biological contextrepresentation may include sequences of ingredients for the drugcompounds. The results may include information indicating levels ofcertain types of activity associated with certain design spaces. In oneembodiment, the results may include causal inference informationpertaining to whether certain ingredients in the drug compounds arecorrelated with or determined by certain effects (e.g., activity levels)in the design space.

The one or more machine learning models 132 may refer to model artifactscreated by the training engine 130 using training data that includestraining inputs and corresponding target outputs. The training engine130 may find patterns in the training data wherein such patterns map thetraining input to the target output and generate the machine learningmodels 132 that capture these patterns. Although depicted separatelyfrom the server 128, in some embodiments, the training engine 130 mayreside on server 128. Further, in some embodiments, the artificialintelligence engine 140, the database 150, or the training engine 130may reside on the computing device 102.

As described in more detail below, the one or more machine learningmodels 132 may comprise, e.g., a single level of linear or non-linearoperations (e.g., a support vector machine (SVM)) or the machinelearning models 132 may be a deep network, i.e., a machine learningmodel comprising multiple levels of non-linear operations. Examples ofdeep networks are neural networks, including generative adversarialnetworks, convolutional neural networks, recurrent neural networks withone or more hidden layers, and fully connected neural networks (e.g.,each artificial neuron may transmit its output signal to the input ofthe remaining neurons, as well as to itself). For example, the machinelearning model may include numerous layers or hidden layers that performcalculations (e.g., dot products) using various neurons. In someembodiments, one or more of the machine learning models 132 may betrained to use causal inference and counterfactual s.

For example, the machine learning model 132 trained to use causalinference may accept one or more inputs, such as (i) assumptions, (ii)queries, and (iii) data. The machine learning model 132 may be trainedto output one or more outputs, such as (i) a decision as to whether aquery may be answered, (ii) an objective function (also referred to asan estimand) that provides an answer to the query for any received data,and (iii) an estimated answer to the query and an estimated uncertaintyof the answer, where the estimated answer is based on the data and theobjective function, and the estimated uncertainty reflects the qualityof data (i.e., a measure which takes into account the degree or salienceof incorrect data or missing data). The assumptions may also be referredto as constraints and may be simplified into statements used in themachine learning model 132. The queries may refer to scientificquestions for which the answers are desired.

The answers estimated using causal inference by the machine learningmodel may include optimized sequences of ingredients in selectedcandidate drug compounds. As the machine learning model estimatesanswers (e.g., candidate drug compounds), certain causal diagrams may begenerated, as well as logical statements, and patterns may be detected.For example, one pattern may indicate that “there is no path connectingingredient D and activity P,” which may translate to a statisticalstatement “D and P are independent.” If alternative calculations usingcounterfactuals contradict or do not support that statistical statement,then the machine learning model 132 or the biological contextrepresentation may be updated. For example, another machine learningmodel 132 may be used to compute a degree of fitness which represents adegree to which the data is compatible with the assumptions used by themachine learning model that uses causal inference. There are certaintechniques that may be employed by the other machine learning model 132to reduce the uncertainty and increase the degree of compatibility. Thetechniques may include those for maximum likelihood, propensity scores,confidence indicators, or significance tests, among others.

In some embodiments, a generative adversarial network (GAN) may generatea set of candidate drug compounds without using causal inference. Insome embodiments, the GAN may generate a set of candidate drug compoundsusing causal inference. A GAN refers to a class of deep learningalgorithms including two neural networks, a generator and adiscriminator, that both compete with one another to achieve a goal. Forexample, regarding candidate drug compound generation, the generatorgoal may include generating candidate drug compounds, includingcompatible/incompatible sequences of ingredients, andeffective/ineffective sequences of ingredients, etc. that thediscriminator classifies as feasible candidate drug compounds, includingcompatible and effective sequences of ingredients that may producedesired activity levels for a design space. In one embodiment, thegenerator may use causal inference, including counterfactuals, tocalculate numerous alternative scenarios that indicate whether a certainresult (e.g., activity level) still follows when any element or aspectof a sequence changes. For example, the generator may be a neuralnetwork based on Markov models (e.g., Deep Markov Models), which mayperform causal inference. In some embodiments, one or more of thecounterfactuals used during the causal inference may be determined andprovided by the scientist module. The discriminator goal may includedistinguishing candidate drug compounds which include undesirablesequences of ingredients from candidate drug compounds which includedesirable sequences of ingredients.

In some embodiments, the generator initially generates candidate drugcompounds and continues to generate better candidate drug compoundsafter each iteration until the generator eventually begins to generatecandidate drug compounds that are valid drug compounds which producecertain levels of activity within a design space. A candidate drugcompound may be “valid” when it produces a certain level ofeffectiveness (e.g., above a threshold activity level as determined by astandard (e.g., regulatory entity)) in a design space. In order toclassify the candidate drug compounds as a valid drug compound orinvalid candidate drug compound, the discriminator may receive real drugcompound information from a dataset and the candidate drug compoundsgenerated by the generator. “Real drug compound,” as used in thisdisclosure, may refer to a drug compound that has been approved by anyregulatory (governmental) body or agency. The generator obtains theresults from the discriminator and applies the results in order togenerate better (e.g., valid) candidate drug compounds.

General details regarding the GAN are now discussed. The two neuralnetworks, the generator and the discriminator, may be trainedsimultaneously. The discriminator may receive an input and then output ascalar indicating whether a candidate drug compound is an actual orviable drug compound. In some embodiments, the discriminator mayresemble an energy function that outputs a low value (e.g., close to 0)when input is a valid drug compound and a positive value when the inputis not a valid drug compound (e.g., if it includes an incorrect sequenceof ingredients for certain activity levels pertaining to a designspace).

There are two functions that may be used, the generator function (G(V)),and the discriminator function (D(Y)). The generator function may bedenoted as G(V), where V is generally a vector randomly sampled in astandard distribution (e.g., Gaussian). The vector may be any suitabledimension and may be referred to as an embedding herein. The role of thegenerator is to produce candidate drug candidates to train thediscriminator function (D(Y)) to output the values indicating thecandidate drug candidate is valid (e.g., a low value), where Y isgenerally a vector referred to as an embedding and where, further, Y mayinclude candidate drug compounds or real drug compounds.

During training, the discriminator is presented with a valid drugcompound and adjusts its parameters (e.g., weights and biases) to outputa value indicative of the validity of the candidate drug compounds thatproduce real activity levels in certain design spaces. Next, thediscriminator may receive a modified candidate drug compound (e.g.,modified using counterfactuals) generated by the generator and adjustits parameters to output a value indicative of whether the modifiedcandidate drug compound provides the same or a different activity levelin the design space.

The discriminator may use a gradient of an objective function toincrease the value of the output. The discriminator may be trained as anunsupervised “density estimator,” i.e., a contrast function produces alow value for desired data (e.g., candidate drug compounds that includesequences producing desired levels of certain types of activity in adesign space) and higher output for undesired data (e.g., candidate drugcompounds that include sequences producing undesirable levels of certaintypes of activity in a design space). The generator may receive thegradient of the discriminator with respect to each modified candidatedrug compound it produces. The generator uses the gradient to trainitself to produce modified candidate drug compounds that thediscriminator determines include sequences producing desired levels ofcertain types of activity in a design space.

Recurrent neural networks include the functionality, in the context of ahidden layer, to process information sequences and store informationabout previous computations. As such, recurrent neural networks may haveor exhibit a “memory.” Recurrent neural networks may include connectionsbetween nodes that form a directed graph along a temporal sequence.Keeping and analyzing information about previous states enablesrecurrent neural networks to process sequences of inputs to recognizepatterns (e.g., such as sequences of ingredients and correlations withcertain types of activity level). Recurrent neural networks may besimilar to Markov chains. For example, Markov chains may refer tostochastic models describing sequences of possible events in which theprobability of any given event depends only on the state informationcontained in the previous event. Thus, Markov chains also use aninternal memory to store at least the state of the previous event. Thesemodels may be useful in determining causal inference, such as whether anevent at a current node changes as a result of the state of a previousnode changing.

The set of candidate drug compounds generated may be input into anothermachine learning model 132 trained to classify of the set of candidatedrug compounds as a selected candidate drug compound. The classifier maybe trained to rank the set of candidate drug compounds using anysuitable ranking (i.e., for example, non-parametric) technique. Forexample, in some embodiments, one or more clustering techniques may beused to cluster the set of candidate drug compounds. To classify theselected candidate drug compound, the machine learning model 132 mayalso perform objective optimization techniques while clustering. Toclassify the selected candidate drug compound having desired levels ofcertain types of activity, the objective optimization may include usinga minimization or maximization function for each candidate drug compoundin the clusters.

A cluster may refer to a group of data objects similar to one anotherwithin the same cluster, but dissimilar to the objects in the otherclusters. Cluster analysis may be used to classify the data intorelative groups (clusters). One example of clustering may includeK-means clustering where “K” defines the number of clusters. PerformingK-means clustering may comprise specifying the number of clusters,specifying the cluster seeds, assigning each point to a centroid, andadjusting the centroid.

Additional clustering techniques may include hierarchical clustering anddensity based spatial clustering. Hierarchy clustering may be used toidentify the groups in the set of candidate drug compounds where thereis no set number of clusters to be generated. As a result, a tree-basedrepresentation of the objects in the various groups may be generated.Density-based spatial clustering may be used to identify clusters of anyshape in a dataset having noise and outliers. This form of clusteringalso does not require specifying the number of clusters to be generated.

FIG. 1B illustrates an architecture of the artificial intelligenceengine according to certain embodiments of this disclosure. Thearchitecture may include a biological context representation 200, acreator module 151, a descriptor module 152, a scientist module 153, areinforcer module 154, and a conductor module 155. The architecture mayprovide a platform that improves its machine learning models over timeby using benchmark analysis to produce enhanced candidate drug compoundsfor target design spaces. The platform may also continuously orcontinually learn new information from literature, clinical trials,studies, research, or any suitable data source about drug compounds. Thenewly learned information may be used to continuously or continuallytrain the machine learning models to evolve with evolving information.

The biological context representation 200 may be implemented in ageneral manner such that it can be applied to solve different types ofproblems across different markets. The underlying structure of thebiological context representation 200 may include nodes andrelationships between the nodes. There may be semantic information,activity information, structural information, chemical information,pathway information, and so forth represented in the biological contextrepresentation 200. The biological context representation 200 mayinclude any number of layers of information (e.g., five layers ofinformation). The first layer may pertain to molecular structure andphysical property information, the second layer may pertain tomolecule-to-molecule interactions, the third layer may pertain tomolecule pathway interactions, the fourth layer may pertain to moleculecell profile associations, and the fifth layer may pertain totherapeutics (including those using biologics) and indications relevantfor molecules. The biological context representation 200 is discussedfurther below with reference to FIGS. 2 and 5.

Further, to increase computing processing using various encodings, thosevarious encodings may be selected to preferentially represent certaintypes of data. For example, to effectively capture common backbonestructures of molecules, Morgan fingerprints may be used to describephysical properties of the candidate drug compounds. The encodings arediscussed further below with reference to FIG. 1G.

Although just one creator module 151 is depicted, there may any suitablenumber of creator modules 151. Each of the creator modules 151 mayinclude one or more generative machine learning models trained togenerate new candidate drug compounds. The new candidate drug compoundsare then added to the biological context representation 200. To thatend, the term “creator module” and “generative model” may be usedinterchangeably herein. Each node in the biological contextrepresentation 200 may be a candidate drug compound (e.g., a peptidecandidate).

The generative machine learning modules included in the creator module151 may be of different types and perform different functions. Thedifferent types and different functions may include a variationalautoencoder, structured transformer, Mini Batch Discriminator, dilation,self-attention, upsampling, loss, and the like. Each of these generativemachine learning model types and functions is briefly explained below.

Regarding the variational autoencoder, it may simultaneously train twomachine learning models, an inference model q_(φ)(z|x) and a generativemodel p_(θ)(x|z)p_(θ)(z) for data x and a latent variable z. In someembodiments, both the inference model and the generative model may beconditioned on a chosen attribute of the sequences. Both models may bejointly optimized using a tractable variational Bayesian approach whichmaximizes an evidence lower bound (ELBO)

Regarding the structured transformer, it may perform autoregressivedecomposition to decompose the joint probability distribution of thesequence given the structure p=(s|x) autoregressively as:

p(s|x)=π_(i) p(s _(i) |x _(<i))

The conditional probability p(s_(i)|x_(<i)) of amino acid s_(i) atposition i is conditioned on both the input structure x and thepreceding amino acid s_(i) and the preceding amino acid s_(<1)={s₁, . .. s^(i) _(i−1)}. These conditionals may be parameterized in terms of twosub-networks: an encoder that computes embeddings from structure-basedfeatures and edge features, and a decoder that autoregressively predictsamino acid letter s_(i) given the preceding sequence and structuralembeddings from the encoder.

Mode collapse occurs in generative adversarial networks when thegenerator generates a limited diversity of samples, or even the samesample, regardless of the input. To overcome mode collapse, someembodiments implement a Mini Batch Discriminator (MBD) approach. MBDseach work as an extra layer in the network that computes the standarddeviation across the batch of examples (the batch contains only realdrug compounds or only candidate drug compounds). If the batch containsa small variety of examples, the standard deviation will be low, and thediscriminator will be able to use this information to lower the scorefor each example in the batch. To further reduce mode collapseoccurrence, some embodiments balance the sampling frequency of thetraining dataset clusters.

Regarding dilation, convolution filters may be capable of detectinglocal features, but they have limitations when it comes to relationshipsseparated by long distances. Accordingly, some embodiments implementconvolution filters with dilation. By introducing gaps into convolutionkernels, such techniques increase the receptive field without increasingthe number of parameters. Dilation rate may be applied to oneconvolution filter in each residual block of a generator or adiscriminator. In this way, by the last layer of the generativeadversarial network, filters may include a large enough receptive fieldto learn relationships separated by long-distances. Residual blocks arediscussed further below with reference to FIG. 1F.

Regarding self-attention, different areas of a protein have differentassociations and effects on overall protein behavior. Accordingly, thearchitecture of the generative adversarial network disclosed hereinimplements a self-attention mechanism. The self-attention mechanism mayinclude a number of layers that highlight different areas of importanceacross the entire sequence and allow the discriminator to determinewhether parts in distant portions of the protein are consistent witheach other.

Regarding upsampling, some embodiments implement techniques best suitedfor protein generation. For example, nearest-neighbor interpolation,transposed convolution, and sub-pixel convolution may be used. Sub-pixelshuffle convolution may be used to increase resolution of a design spaceduring candidate drug compound generation. Any combination of thesetechniques may be used in the upsampling layers. In some embodiments,transposed convolution by itself may be used for all upsampling layers.

Regarding the loss function, it is a component that aids in thesuccessful performance of a neural network. Various losses, such asnon-saturating, non-saturating with R1 regularization, hinge, hinge withrelativistic average, and Wasserstein and Wasserstein with gradientpenalty losses, may be used. In some embodiments, due to performanceincreases, the non-saturating loss with R1 regularization may be usedfor the generative adversarial network.

Details pertaining to the architecture of the creator module 151 aredescribed below with reference to FIGS. 1C-1I.

The descriptor module 152 may include one or more machine learningmodels trained to generate descriptions for each of the candidate drugcompounds generated by the creator module 151. The descriptor module 152may be trained to use different encodings to represent the differenttypes of information included in the candidate drug compound. Thedescriptor module 152 may populate the information in the candidate drugcompound with ordinal values, cardinal values, categorical values, etc.depending on the type of information. For example, the descriptor module152 may include a classifier that analyzes the candidate drug compoundand determines whether it is a cancer peptide, an antimicrobial peptide,or a different peptide. The descriptor module 152 describes thestructure and the physiochemical properties of the candidate drugcompound.

The reinforcer module 154 may include one or more machine learningmodels trained to analyze, based on the descriptions, the structure andthe physiochemical properties of the candidate drug compounds in thebiological context representation 200. Based on the analysis, thereinforcer module 154 may identify a set of experiments to perform onthe candidate drug compounds to elicit certain desired data (e.g.,activity effectiveness, biomedical features, etc.). The identificationmay be performed by matching a pattern of the structure andphysiochemical properties of the candidate drug compounds with thestructure and physiochemical properties of other drug compounds anddetermining which experiments were performed on the other drug compoundsto elicit desired data. The experiments may include in vitro or in vivoexperiments. Further, the reinforcer module 154 may identify experimentsthat should not be performed for the candidate drug compounds if adetermination is made that those experiments yield useless data for drugcompounds.

The conductor module 155 may include one or more machine learning modelstrained to perform inference queries on the data stored in thebiological context representation 200. The inference queries may pertainto performing queries to improve the quality of the data in thebiological context representation 200. For example, there may be a gapin data in one of the nodes (e.g., candidate drug compounds) stored inthe biological context representation 200. An inference query refers tothe process of identifying a first node and a second node similar to thefirst node, and to obtaining data from the second node to fill a datagap in the first node. An inference query may be executed to search foranother node having similarities to the node with the gap and may fillthe gap with the data from the other node.

The scientist module 153 may include one or more machine learning modelstrained to perform benchmark analysis to evaluate various parameters ofthe creator module 151. In some embodiments, the scientist module 153may generate scores for the candidate compound drugs generated by thecreator module 151. The benchmark analysis may be used to electronicallyand recursively optimize the creator module 151 to generate candidatedrug compounds having improved scores in subsequent generation rounds.There may be several types of benchmarks (e.g., distribution learningbenchmarks, goal-directed benchmarks, etc.) used by the scientist module153 to evaluate generative machine learning models used by the creatormodule 151. As described herein, one or more parameters (e.g., validity,uniqueness, novelty, Frechet ChemNet Distance (FCD), internal diversity,Kullback-Leibler (KL) divergence, similarity, rediscovery, isomercapability, median compounds, etc.) of the creator module 151 may bescored during benchmark analysis. The benchmark analysis may also beused to electronically and recursively optimize the creator module 151to improve scores of the parameters in subsequent generation rounds. Anycombination of the benchmarks described below may be used to evaluatethe creator module 151.

One type of benchmark used by the scientist module 153 may include adistribution learning benchmark. The distribution learning benchmarkevaluates, when given a set of molecules, how well the creator module151 generates new molecules which follow the same chemical distribution.For example, when provided with therapeutic peptides, the distributionlearning benchmark evaluates how well the creator module 151 generatesother therapeutic peptides having similar chemical distributions.

The distribution learning benchmark may include generating a score foran ability of the creator module 151 to generate valid candidate drugcompounds, a score for an ability of the creator module 151 to generateunique candidate drug compounds, a score for an ability of the creatormodule 151 to generate novel candidate drug compounds, a Frechet ChemNetDistance (FCD) score for the creator module 151, an internal diversityscore for the creator module 151, a KL divergence score for the creatormodule 151, and so forth. Each of the distribution learning benchmarksis now discussed.

The validity score may be determined as a ratio of valid candidate drugcompounds to non-valid candidate drug compounds of generated candidatedrug compounds. In some embodiments, the ratio may be determined from acertain number (e.g., 10,000) of candidate drug compounds. In someembodiments, candidate drug compounds may be considered valid if theirrepresentation (e.g., simplified molecular-input line-entry system(SMILES)) can be successfully parsed using any suitable parser.

The uniqueness score may be determined by sampling candidate drugcompounds generated by the creator module 151 until a certain number(e.g., 10,000) of valid molecules are identified by identicalrepresentations (e.g., canonical SMILES strings). The uniqueness scoremay be determined as the number of different representations divided bythe certain number (e.g., 10,000).

The novelty score may be determined by generating candidate drugcompounds until a certain number (e.g., 10,000) of differentrepresentations (e.g., canonical SMILES strings) are obtained andcomputing the ratio of candidate drug compounds (including real drugcompounds) not present in the training dataset.

The Frechet ChemNet Distance (FCD) score may be determined by selectinga random subset of a certain number (e.g., 10,000) of drug compoundsfrom the training dataset, and generating candidate drug compounds usingthe creator module 151 until a certain number (10,000) of validcandidate drug compounds are obtained. The FCD between the subset of thedrug compounds and the candidate drug compounds may be determined. TheFCD may consider chemically and biologically relevant information aboutdrug compounds, and also measure the diversity of the set via thedistribution of generated candidate drug compounds. The FCD may detectif generated candidate drug compounds are diverse, and the FCD maydetect if generated candidate drug compounds have similar chemical andbiological properties as real drug compounds. The FCD score (“S”) isdetermined using the following relationship: S=exp(−0.2*FCD).

The internal diversity score may assess the chemical diversity within aset of generated candidate drug compounds (“GROUP”). The internaldiversity score may be determined using the following relationship:

${{IntDiv}_{p}(G)} = {1 - \sqrt[p]{\frac{1}{{G}^{2}}\Sigma_{\{{m_{1},{m_{2} \in G}}\}}{T\left( {m_{1},m_{2}} \right)}^{p}}}$

In the equation in [0067], T(m₁, m₂) is the Tanimoto Similarity (SNN)between molecule 1, m₁, and molecule 2, m₂. Variable G is the set ofcandidate drug compounds and variable p is the set number of groupsbeing tested. While SNN measures the dissimilarity to externaldiversity, the internal diversity score may consider dissimilaritybetween generated candidate drug compounds. The internal diversity scoremay be used to detect mode collapse in certain generative models. Forexample, mode collapse may occur when the generative model produces alimited variety of candidate drug compounds while ignoring some areas ofa design space. A higher score for the internal diversity corresponds tohigher diversity in the set of candidate drug compounds generated.

The KL divergence score may be determined by calculating physiochemicaldescriptors for both the candidate drug compounds and the real drugcompounds. Further, a determination may be made of the distribution ofmaximum nearest neighbor similarities on fingerprints (e.g., extendedconnectivity fingerprint of up to four bonds (ECFP4)) for both thecandidate drug compounds and the real drug compounds. The distributionof these descriptors may be determined via kernel density estimation forcontinuous descriptors, or as a histogram for discrete descriptors. TheKL divergence D_(KL,i) may be determined for each descriptor i, and isaggregated to determine the KL divergence score S via:

$S = {\frac{1}{k}\Sigma_{i}^{k}\mspace{14mu}{\exp\left( {- D_{{KL},i}} \right)}}$

Where k is the number of descriptors (e.g., k=9).

The isomer capability score may be determined by whether molecules maybe generated that correspond to a target molecular formula (for exampleC7H8N2O2). The isomers for a given molecular formula can in principle beenumerated, but except for small molecules this number will in generalbe very large. The isomer capability score represents fully-determinedtasks that assess the flexibility of the creator module to generatemolecules following a simple pattern (which is a priori unknown).

A second type of benchmark may include a goal-directed benchmark. Thegoal-direct benchmark may evaluate whether the creator module 151generates a best possible candidate drug compound to satisfy apre-defined goal (e.g., activity level in a design space). A resultingbenchmark score may be calculated as a weighted average of the candidatedrug compound scores. In some embodiments, the candidate drug compoundswith the best benchmark scores may be assigned a larger weight. As such,generative models of the creator module 151 may be tuned to deliver afew candidate drug compounds with top scores, while also generatingcandidate drug compounds with satisfactory scores. For each of thegoal-directed benchmarks, one or several average scores may bedetermined for the given number of top candidate drug compounds and thenthe resulting benchmark score may be calculated as the mean of theseaverage scores. For example, the resulting benchmark score may be acombination of the top-1, top-10, and top-100 scores, in which theresulting benchmark score is determined by the following relationship:

${{IntDiv}_{p}(G)} = {1 - \sqrt[p]{\frac{1}{{G}^{2}}\Sigma_{m_{1},{m_{2 \in}G}}{T\left( {m_{1},m_{2}} \right)}^{p}}}$

Where s is an n-dimensional (e.g., 100-dimensional) vector of candidatedrug compound scores s_(v)1<i<100 sorted in decreasing order (e.g.,s_(i)≥s_(j) for i<j). Variable G is the set of candidate drug compoundsand variable p is the set number of groups being tested.

The goal-directed benchmark may include generating a score for anability of the creator module 151 to generate candidate drug compoundssimilar to a real drug compound, a score for an ability of the creatormodule 151 to rediscover the potential viability of previously-knowndrug compounds (e.g., using a drug which is prescribed for certainconditions for a new condition or disease), and the like.

The similarity score may be determined using nearest neighbor scoring,fragment similarity scoring, scaffold similarity scoring, SMARTSscoring, and the like. Nearest neighbor scoring (e.g., nns(G, R)) mayrefer to a scoring function that determines the similarity of thecandidate drug compound to a target real drug compound g. The scorecorresponds to the Tanimoto similarity when considering the fingerprintr and may be determined by the following relationship:

${{NNS}\left( {G,R} \right)} = {\frac{1}{G}\Sigma_{m_{G}\mspace{14mu}{in}\mspace{14mu} G}^{\max}\mspace{14mu}{T\left( {m_{G}m_{R}} \right)}}$

Where m_(R) and m_(G) are representations of the real drug compounds (R)and the candidate drug compounds (G) as bit strings (e.g., digitalfingerprints, e.g., outputs of hash functions, etc.). The resultingscore reflects how similar candidate drug compounds are to real drugcompounds in terms of chemical structures encoded in these fingerprints.In some embodiments, Morgan fingerprints may be used with a radius of aconfigurable value (e.g., 2) and an encoding with a configurable numberof bits (e.g., 1024). The radius and encoding bits may be configured toproduce desirable results in a biochemical space.

The similarity score may be determined using fragment similarityscoring, which itself may be defined as the cosine distance betweenvectors of fragment frequencies. For a set of candidate drug compounds(G), its fragment frequency vectorfG has a size equal to the size of allchemical fragments in the dataset, and elements of fG representfrequencies with which the corresponding fragments appear in G. Thedistance is determined by the following relationship:

Frag(G, R)=1−cos(f_(G)f_(R))

Candidate drug compounds and real drug compounds may be fragmented usingany suitable decomposition algorithm. The fragment similarity scoringscore represents the similarity of the set of candidate drug compoundsand the set of real drug compounds at the level of chemical fragments.

The similarity score may be determined using scaffold similarityscoring, which may be determined in a similar way to the fragmentsimilarity scoring. For example, the scaffold similarity scoring may bedetermined as a cosine similarity between the vectors S_(G) and S_(R)that represent frequencies of scaffolds in a set of candidate drugcompounds (G) and a set of real drug compound (R). The scaffoldsimilarity scoring score may be determined by the followingrelationship:

Frag(G,R)=1−cos(s_(G)s_(R)).

The similarity score may be determined using SMARTS scoring. SMARTSscoring may be implemented according to the relationship: SMART (a, b).The SMARTS scoring may evaluate whether the SMARTS pattern s is presentin a candidate drug compound. $b$ is a Boolean value indicating whetherthe SMARTS pattern should be present (true) or absent (false). When thepattern is desired, a score of 1, for true, is returned if the SMARTSpattern is found. If the pattern is not found, then a score of 0, forfalse, is returned.

In some embodiments, a goal-directed benchmark may include determining arediscovery score for the creator module 151. In some embodiments,certain real drug compounds may be removed from the training dataset andthe creator module 151 may be retrained using the modified training setlacking the removed real drug compounds. If the creator module 151 isable to generate (“rediscover”) a candidate drug compound that isidentical or substantially similar to the removed real drug compounds,then a high rediscovery score may be assigned. Such a technique may beused to validate the creator module 151 is effectively trained or tuned.

Various modifiers may be used to modify the scores for the variousbenchmarks discussed above. For example, a Gaussian modifier may beimplemented to target a specific value of some property, while givinghigh scores when the underlying value is close to the target. It may beadjustable as desired. A minimum Gaussian modifier may correspond to theright half of a Gaussian function and values smaller than a thresholdmay be given a full score, while values larger than the thresholddecrease continuously to zero. A maximum Gaussian modifier maycorrespond to a left half of the Gaussian function and values largerthan the threshold are given a full score, while values smaller than thethreshold decrease continuously to zero. A threshold modifier mayattribute a full score to values above a given threshold, while valuessmaller than the threshold decrease linearly to zero.

There are a variety of competing generative models that may be used toevaluate the performance of the creator module 151. For example, thecompeting generative models may include a random sampling, best ofdataset method, SMILES genetic algorithm (GA), graph GA, graphMonte-Carlo tree search (MCTS), SMILES long short-term memory (LSTM),character-level recurrent neural networks (CharRNN), variationalautoencoder, adversarial autoencoder, Latent generative adversarialnetwork (LatentGAN), junction tree variational autoencoder (JT-VAE), andobjective-reinforced generative adversarial network (ORGAN). Each ofthese competing generative models will now be discussed briefly.

Regarding random sampling, this baseline samples at random the requestednumber of molecules (candidate drug compounds) for the dataset. Randomsampling may provide a lower bound for the goal-directed benchmarks,because no optimization is performed to obtain the returned molecules.Random sampling may provide an upper bound for the distribution learningbenchmarks, because the molecules returned may be taken directly for theoriginal distribution.

Regarding best of dataset method (or “best of dataset” herein), one goalof de novo molecular design is to explore unknown parts of thebiochemical space, generating new candidate drug compounds with betterproperties than the drug compounds already known. The best of datasetscores the entire generated dataset including the candidate drugcompounds with a provided scoring function and returns the highestscoring molecules. This effectively provides a lower bound for thegoal-directed benchmarks that enables the creator module 151 to createbetter candidate drug compounds than the real or candidate drugcompounds provided.

Regarding SMILES GA, this technique may evolve string molecularrepresentations using mutations exploiting the SMILES context-freegrammar. For each goal-directed benchmark, a certain number (e.g., 300)of highest scoring molecules in the dataset may be selected as aninitial population. In this example, each molecule is represented by 300genes. During each epoch an offspring of a certain number (e.g., 600) ofnew molecules may be generated by randomly mutating the populationmolecules. After deduplication and scoring, these new molecules may bemerged with the current population and a new generation is chosen byselecting the top scoring molecules overall. This process may berepeated a certain number of times (e.g., 1000) or until progress hasstopped for a certain number (e.g., 5) of consecutive epochs.Distribution-learning benchmarks do not apply to this baseline.

Regarding graph GA, this GA involves molecule evolution at the graphlevel. For each goal-directed benchmark a certain number (e.g., 100) ofhighest scoring molecules in the dataset are selected as the initialpopulation. During each epoch, a mating pool of a certain number (e.g.,200) of molecules is sampled with replacement from the population, usingscores as weights. This pool may contain many repeated molecules iftheir score is high. A new population of a certain number (e.g., 100) isthen generated by iteratively choosing two molecules at random from themating pool and applying a crossover operation. With probability of,e.g., 0.5 (i.e., 100/200), a mutation is also applied to the offspringmolecule. This process is repeated a certain number (e.g., 1000) oftimes or until progress has stopped for a certain number (e.g., 5) ofconsecutive epochs. Distribution-learning benchmarks do not apply tothis baseline.

Regarding graph MCTS, the statistics used during sampling may becomputed on the training dataset. For this baseline, no initialpopulation is selected for the goal-directed benchmarks. Each newmolecule may be generated by running a certain number (e.g., 40) ofsimulations, starting from a base molecule. At each step, a certainnumber (e.g., 25) of children are considered and the sampling stops whenreaching a certain number (e.g., 60) of atoms. The best-scoring moleculefound during the sampling may be returned. A population of a certainnumber (e.g., 100) of molecules is generated at each epoch. This processmay be repeated a certain number (e.g., 1000) of times or until progresshas stopped for a certain number (e.g., 5) of consecutive epochs. Forthe distribution learning benchmark. the generation starts from a basemolecule and a new molecule is generated with the same parameters. Asfor the goal-directed benchmarks, the only difference is that no scoringfunction is provided, so the first molecule to reach terminal state isreturned instead of the highest scoring molecule.

Regarding SMILES LSTM, the technique is a baseline model, consisting ofan LSTM neural network which predicts the next character of partialSMILES strings. In some embodiments, a SMILES LSTM may be used with 3layers of hidden size of 1024. For the goal-directed benchmarks, acertain number (e.g., 20) of iterations of hill-climbing may beperformed; at each step the model generated a certain number (e.g.,8192) of molecules and a certain number (e.g., 1024) of the top scoringmolecules may be used to fine-tune the model parameters. For thedistribution-learning benchmark, the model may generate the requestednumber of molecules.

Regarding character-level recurrent neural networks (CharRNN), thetechnique treats the task of generating SMILES as a language modelattempting to learn the statistical structure of SMILES syntax bytraining it on a large corpus of SMILES. The CharRNN parameters may beoptimized using maximum likelihood estimation (MLE). In someembodiments, CharRNN may be implemented using LSTM RNN cells stackedinto a certain number of layers (e.g., 3 layers) with a certain numberof hidden dimensions (e.g., 600 hidden dimensions) . In someembodiments, to prevent overfitting, a dropout layer may be addedbetween intermediate layers with a certain dropout probability (e.g.,p=0.2). Training may be performed with a batch size of a certain number(e.g., 64) using an optimizer.

Regarding a variational autoencoder (VAE), it is a framework fortraining two neural networks, an encoder and a decoder, to learn amapping from a higher-dimensional data representation (e.g., vector)into a lower-dimensional data representation and from thelower-dimensional data representation back to the higher-dimensionaldata representation. The lower-dimensional space is called the latentspace, which is often a continuous vector space with normallydistributed latent representation. The latent representation of our datamay contain all the important information needed to represent anoriginal data point. The latent representation represents the featuresof the original data point. In other words, one or more machine learningmodels may learn the data features of the original data point andsimplify its representation to make it more efficient to analyze. VAEparameters may be optimized to encode and decode data by minimizing thereconstruction loss while also minimizing a KL-divergence term arisingfrom the variational approximation, such that the KL-divergence term mayloosely be interpreted as a regularization term. Since molecules arediscrete objects, properly trained VAE defines an invertible continuousrepresentation of a molecule.

In some embodiments, aspects from both implementations may be combined.The encoder may implement a bidirectional Gated Recurrent Unit (GRU)with a linear output layer. The decoder may be a 3-layer GRU RNN of 512hidden dimensions with intermediate dropout layers, the layers having adropout probability of 0.2. Training may be performed with a batch sizeof a certain number (e.g., 128), utilizing a gradient clipping of 50 anda KL-term weight of 1, and further optimized with a learning rate of0.0003 across 50 epochs. Other training parameters may be used toperform the embodiments disclosed herein.

Regarding adversarial autoencoders (AAE), they combine the idea of VAEwith that of adversarial training as found in a GAN. In AAE, the KLdivergence term is avoided by training a discriminator network topredict whether a given sample came from the latent space of the AE orfrom a prior distribution of the autoencoder (AE). Parameters may beoptimized to minimize the reconstruction loss and to minimize thediscriminator loss. The AAE model may consist of an encoder with a1-layer bidirectional LSTM with 380 hidden dimensions, a decoder with a2-layer LSTM with 640 hidden dimensions and a shared embedding of size32. The latent space is of 640 dimensions, and the discriminatornetworks is a 2-layer fully connected neural network with 640 and 256nodes respectively, utilizing the ELU activation function. Training maybe performed with a batch size of 128, with an optimizer using alearning rate of 0.001 across 25 epochs. Other training parameters maybe used to perform the embodiments disclosed herein.

Regarding LatentGAN, the technique encodes SMILES strings into latentvector representations of size 512. A Wasserstein Generative Adversarialnetwork with Gradient Penalty may be trained to generate latent vectorsresembling that of the training set, which are then decoded using aheteroencoder.

Regarding a junction tree variational autoencoder (JT-VAE), the modelgenerates molecular graphs in two phases. The model first generates atree-structured scaffold over chemical substructures, and then combinesthem into a molecule with a graph message passing network. This approachenables incrementally expanding molecules while maintaining chemicalvalidity at every step.

Regarding an objective-reinforced generative adversarial network(ORGAN), the model is a sequence-generation model based on adversarialtraining that aims at generating discrete sequences that emulate a datadistribution while using reinforcement learning to bias the generationprocess towards some desired objective rewards. ORGAN incorporates atleast 2 networks: a generator network and a discriminator network. Thegoal of the generator network is to create candidate drug compoundsindistinguishable from the empirical data distribution of real drugcompounds. The discriminator exists to learn to distinguish a candidatedrug compound from real data samples. Both models are trained inalternation.

To properly train a GAN, the gradient must be back-propagated betweenthe generator and discriminator networks. Reinforcement uses an N-depthMonte Carlo tree search, and the reward is a weighted sum ofprobabilities from the discriminator and objective reward. Both thegenerator and discriminator may be pre-trained for 250 and 50 epochs,respectively, and then jointly trained for 100 epochs utilizing anoptimizer with a learning rate of 0.0001. The learning rate may refer toa hyperparameter of a neural network, and the learning rate may be anumber that determines an amount of change (e.g., weights, hiddenlayers, etc.) to make to a machine learning model in response to anestimated error. Bayesian optimization may be used to determine theoptimal learning rate during training of a particular neural network. Insome embodiments, validity and uniqueness of candidate drug compoundsmay be used as rewards.

The scientist module 153 may also include one or more machine learningmodels trained to perform causal inference using counterfactuals. Thecausal inference, as described herein, may be used to determine whetherthe creator module 151 actually generated a candidate drug candidate,including a desired activity in such candidate, or if it was determinedbecause of noisy data (e.g., scarce or incorrect data).

FIG. 1C illustrates first components of an architecture of the creatormodule 151 according to certain embodiments of this disclosure. Acandidate design space 156 and data 157 may be included in thebiological context representation 200, such space 156 and data 157 toinclude the various sequences of the candidate drug compounds or realdrug compounds. In some embodiments, the creator module 151 may populatethe candidate design space 156. The candidate design space 156 mayinclude a vast amount of information retrieved from numerous sources orgenerated by the AI engine 140. The candidate design space 156 mayinclude information pertaining to antimicrobial peptides, anticancerpeptides, peptidomimetics, uProteins and aCRFs, non-ribosomal peptides,and general peptides that are retrieved via genomic screening,literature research, or computationally designed using the AI engine140. The candidate design space 156 may be updated each time the creatormodule 151 generates a new candidate drug compound. The candidate designspace 156 may also be updated continuously or continually as newliterature is published or genomic screenings are performed.

The creator module 151 may also use data 157 to generate the candidatedrug compounds. In some embodiments, the data 157 may be generated orprovided by the descriptor module 152. In some embodiments, the data maybe received from any suitable source. The data may include molecularinformation pertaining to chemistry/biochemistry, targets, networks,cells, clinical trials, market (e.g., analysis, results, etc.) thatresult from performing simulations or experiments.

The creator module 151 may encode the candidate design space 156 and thedata 157 into various encodings. In some embodiments, an attentionmessage-passing neural network may be used to encode molecular graphs.An initial set of states may be constructed, one for each node in amolecular graph. Then, each node may be allowed to exchange information,to “message” with its neighboring nodes. Each message may be a vectordescribing an atom of a molecule from the atom's perspective in themolecule. After one such step, each node state will contain an awarenessof its immediate neighborhood. Repeating the step makes each node awareof its second-order neighborhood, and so forth. During themessage-passing stage and based on the total number of occurrences of amessage, an attention layer may be used to identify interesting featuresof a molecule. A certain weight (e.g., heavy, light) may be assigned toa message that occurs more or fewer than a threshold number of times,thereby causing that message to stand out more when the messages areaggregated. For example, a message that occurs a very small number oftimes (e.g., less than a threshold) may be more likely to include adesirable feature as opposed to a message that occurs a large number oftimes. In another example, a message that occurs more than a thresholdnumber of times may be weighted more heavily than a message that occursfewer than the threshold number of times. Any suitable weighting may beconfigured to cause a message to stand out more.

Using a summation function to reduce the size of the messages andincrease computational efficiency, the attention mechanism may aggregatethe messages with their weights. In such a way, the techniques may beable to scale to remain computationally efficient as the number ofmessages increases. Such a technique may be beneficial because itreduces resource (e.g., processing, memory) consumption when performingcomputations with a large design space, including information in thatdesign space pertaining to structure, semantic, sequence, physiochemicalproperties, etc.

After a chosen number of “messaging rounds”, all the context-aware nodestates are collected and converted to a summary representing the wholegraph. All the transformations in the steps above may be carried outwith machine learning models (e.g., neural networks), yielding a machinelearning model that can be trained with known techniques to optimize thesummary representation for the current task. The following relationshipsmay be used by the attention message-passing neural network:

     1.  Message  Passing     m_(v)^((t)) = A_(t)(h_(v)^((t)), S_(v)^((t))), where     S_(v)^((t)) = {(h_(w)^((t)), e_(vw))❘w ∈ N(v)}${A_{t}\left( {h_{v}^{(t)},\left\{ \left( {h_{w}^{(t)},e_{vw}} \right) \right\}} \right)} = {\sum\limits_{w \in {N{(v)}}}{{f_{NN}^{(e_{vw})}\left( h_{w}^{(t)} \right)} \odot \frac{\exp\left( {g_{NN}^{(e_{vw})}\left( h_{w}^{(t)} \right)} \right)}{\Sigma_{w^{\prime} \in {N{(v)}}}\mspace{14mu}{\exp\left( {g_{NN}^{(e_{{vw}^{\prime}})}\left( h_{w^{\prime}}^{(t)} \right)} \right)}}}}$     2.  Node  Update     h_(v)^((t + 1)) = u_(t)(h_(v)^((t)), m_(v)^((t)))      3.  Readout     ŷ = R{(h_(v)^((K))❘v ∈ G})

m^((t)) _(v) is the message function, A_(t) is the attention function,U_(t) is the node update function, N(v) is the set of neighbors of nodev in graph G, h^((t)) _(v) is the hidden state of node v at time t, andm^((t)) _(v) is a corresponding message vector. For each atom v,messages will be passed from its neighbors and aggregated as the messagevector m^((t)) from its surrounding environment. Then the hidden stateh^((t)) _(v) is updated by the message vector.

y{circumflex over ( )} is a resulting fixed-length feature vectorgenerated for the graph, and R is a readout function invariant to nodeordering, a feature allowing the MPNN framework to be invariant to graphisomorphism. The graph feature vector y{circumflex over ( )} then ispassed to a fully connected layer to give prediction. All functionsM_(t), U_(t), and R are neural networks, and their weights are learnedduring training.

As depicted, a “Candidates Only Data” encoding 158 may encode just theinformation from the candidate design space, a “Candidates and SimulatedData” encoding 159 may encode information from the candidate designspace 156 and the simulated data from the data 157, and a “Candidateswith All Data” encoding 160 may encode information from the candidatedesign space 156 and both the simulated and experimental data from thedata 157. Further, a “Heterologous Networks” encoding 161 may begenerated using the “Candidates with All Data” encoding 160. Theencodings 158, 159, 160, and 161 may include information pertaining tomolecular structure, physiochemical properties, semantics, and so forth.

Each of the encodings 158, 159, 160, and 161 may be input into aseparate machine learning model trained to generate an embedding. MLModel A, ML Model B, ML Model C, and ML Model D may be included in a“Single Candidate Embedding” Layer.

“Candidates Only Data” encoding 158 may be input into ML Model A, whichoutputs a “Candidate Embedding” 162. “Candidates and Simulated Data”encoding 159 may be input into ML Model B, which outputs a “Candidateand Simulated Data Embedding” 163. “Candidates with All Data” encoding160 may be input into ML Model C, which outputs “Candidate with All DataEmbedding” 164. “Heterologous Networks” encoding 161 may be input intoML Model D, which outputs “Graph and Network Embedding” 165. Theembeddings 162, 163, 164, and 165 may represent information pertainingto a single candidate drug compound.

FIG. 1D illustrates second components of the architecture of the creatormodule 151 according to certain embodiments of this disclosure. Asdepicted, the encodings 158, 159, 160, and 161 are input into ML ModelF, which is trained to output a candidate drug compound based on theencodings 158, 159, 160, and 161.

The embeddings 162, 163, 164, and 165 are input into ML Model G, whichis trained to output a candidate drug compound based on the embeddings162, 163, 164, and 165. In some embodiments, the “Heterologous Networks”161 may be input into ML Model I, which is trained to output a candidatedrug compound based on the “Heterologous Networks” 161. The embeddings162, 163, 164, and 165 are also input into ML Model E in a “KnowledgeLandscape Embedding” layer 167. The ML Model E is trained to output a“Latent Representation” based on the embeddings 162, 163, 164, and 165.

The “Latent Representation” 168 may include an “Activity Landscape” 169and a “Continuous Representation” 170. The “Continuous Representation”170 may include information (e.g., structural, semantic, etc.)pertaining to all of the molecules (e.g., real drug compounds andcandidate drug compounds), and the “Activity Landscape” 169 may includeactivity information for all of the molecules. In some embodiments, theML Model E may be a variational autoencoder that receives the embeddings162, 163, 164, and 165 and outputs lower-dimensional embeddings that aremachine-readable and less computationally expensive for processing. Thelower-dimensional embeddings may be used to generate the “LatentRepresentation” 168. An architecture of the variational autoencoder isdescribed further below with reference to FIG. 1E.

The “Latent Representation” 168 is input into the ML Model H. ML Model Hmay be any suitable type of machine learning model described herein. MLModel H may be trained to analyze the “Latent Representation” 168 andgenerate a candidate drug compound. The “Latent Representation” 168 mayinclude multiple dimensions (e.g., tens, hundreds, thousands) and mayhave a particular shape. The shape may be rectangular, cube, cuboid,spherical, an amorphous blob, conical, or any suitable shape having anynumber of dimensions. The ML Model H may be a generative adversarialnetwork, as described herein. The ML Model H may determine a shape ofthe “Latent Representation” 168 and may determine an area of the shapefrom which to obtain a slice based on “interesting” aspects of thatarea. An interesting aspect may be a peak, valley, a flat portion, orany combination thereof. The ML Model H may use an attention mechanismto determine what is “interesting” and what is not. The interestingaspect may be indicative of a desirable feature, such as a desirableactivity for a particular disease or medical condition. The slice mayinclude a combination of a portion of any of the information included inthe “Latent Representation” 168, such as the structural information,physiochemical properties, semantic information, and so forth. Theinformation included in the slice may be represented as an eigenvectorthat includes any number of dimensions from the “Latent Representation”168. The term “slice” and “candidate drug compound” may be usedinterchangeably. The slice may be visually presented on a displayscreen, as shown in FIG. 8A.

A decoder may be used to transform the slice from the lower-dimensionalvector to a higher-dimensional vector, which may be analyzed todetermine what information is included in that slice. For example, thedecoder may obtain a set of coordinates from the higher-dimensionalvector which may be back-calculated to determine what information (e.g.,structural, physiochemical, semantic, etc.) they represent.

Each of the candidate drug compounds generated by the ML Model F, MLModel G, ML Model H, and ML Model I may be ranked and one of thecandidate drug compounds may be classified as a selected candidate drugcompound, as described herein. Further, the candidate drug compounds maybe input into one or more machine learning models trained to performbenchmark analysis, as described herein. Based on the benchmarkanalysis, any of the machine learning models in the creator module 151may be optimized (e.g., tuning weights, adding or removing hiddenlayers, changing an activation function, etc.) to modify a parameter(e.g., uniqueness, validity, novelty, etc.) score for the machinelearning models when generating subsequent candidate drug compounds.

FIG. 1E illustrates an architecture of a variational autoencoder machinelearning model according to certain embodiments of this disclosure. Insome embodiments, the variational autoencoder may include an inputlayer, an encoder layer, a latent layer, a decoder layer, and an outputlayer. The input layer may receive fingerprints of drug compounds orcandidate drug compounds represented as higher-dimensional vectors, aswell as associated drug concentration(s). The encoder layer may includeone or more hidden layers, activation functions, and the like. Theencoder layer may receive the fingerprint and drug concentration fromthe input layer and may perform operations to translate thehigher-dimensional vectors into lower-dimensional vectors, as describedherein. The latent layer may receive the lower-dimensional vectors andrepresent them in the “Latent Representation” 168. The latent layer mayinput the “Latent Representation” 168 into the ML Model H, which is agenerative adversarial network including a generator and adiscriminator, as described herein. The architecture of the generatorand the discriminator is discussed further below with reference to FIG.1F. The generator generates candidate drug compounds, and thediscriminator analyzes the candidate drug compounds to determine whetherthey are valid or not. The GI in FIG. 1F may refer to a generalinference layer and the GI layer may generate the candidate drugcompounds.

The candidate drug compounds output by the latent layer may be inputinto the decoder layer where the lower-dimensional vectors aretranslated back into the higher-dimensional vectors. The decoder layermay include one or more hidden layers, activation functions, and thelike. The decoder layer may output the fingerprints and the drugconcentration. The output fingerprint and drug concentration may beanalyzed to determine how closely they match the input fingerprint anddrug concentration. If the output and input substantially match, thevariational autoencoder may be properly trained. If the output and theinput do not substantially match, one or more layers of the variationalautoencoder may be tuned (e.g., modify weights, add or remove hiddenlayers).

FIG. 1F illustrates an architecture of a generative adversarial networkused to generate candidate drugs according to certain embodiments ofthis disclosure. As depicted, there is an architecture for thediscriminator, discriminator residual block, generator, and generatorresidual block.

The discriminator architecture may receive a sequence (e.g., candidatedrug compound) as an input. The discriminator architecture may includean arrangement of blocks in a particular order that improvescomputational efficiency when processing the sequence to determinewhether the sequence is valid or not. For example, the particular orderof blocks includes a first residual block, a self-attention block, asecond residual block, a third residual block, a fourth residual block,a fifth residual block, and a sixth residual block. The discriminatormay output a score (e.g., 0 or 1) for whether the received sequence isvalid or not.

The discriminator residual block architecture may receive an inputfiltered into two processing pathways. A first processing pathwayperforms a conversion operation on the input. The second processingpathway performs several operations, including a conversion, a batchnormalization operation, a leaky rectified linear (e.g., ReLu)operation, a conversion operation, and another batch normalizationoperation. The leaky ReLu operation may perform a threshold operation,where any input value less than zero is multiplied by a fixed scalar,for example. The output from the first and second processing pathways issummed and then output.

The generator architecture may receive a noise (e.g., biological contextrepresentation 200) as an input. The generator architecture may includean arrangement of blocks in a particular order that improvescomputational efficiency when processing the noise to generate asequence (e.g., candidate drug compound). For example, the particularorder of blocks includes a first residual block, a second residualblock, a third residual block, a fourth residual block, a fifth residualblock, a self-attention block, and a sixth residual block. The generatormay output a score (e.g., 0 or 1) for whether the received sequence isvalid or not.

The generator residual block architecture may receive an input filteredinto two processing pathways. A first processing pathway performs ade-conversion operation on the input. The second processing pathwayperforms several operations, including a conversion, a batchnormalization operation, a leaky ReLu operation, a de-conversionoperation, and another batch normalization operation. The output fromthe first and second processing pathways is summed and then output.

FIG. 1G illustrates types of encodings to represent certain types ofdrug information according to certain embodiments of this disclosure. Atable 180 includes three columns labeled “Encoding”, “Compressed?”, and“Information”. The “Encoding” column includes rows storing a type ofencoding used to represent a certain type of information; the“Compressed?” column includes rows storing an indication of whether theencoding in that row is compressed; and the “Information” columnincludes rows storing a type of information represented by the encodingin each respective row. The descriptor module 152 may include a machinelearning module trained to analyze a candidate drug compound andidentify various structural properties, physiochemical properties, andthe like. The descriptor module 152 may be trained to represent the typeof structural and physiochemical properties using an encoding thatincreases computational efficiency and to store a description includingthe encodings at a node representing the candidate drug compound. Duringprocessing, the encodings may be aggregated for each candidate drugcompound.

For example, using an alphanumeric string, SMILES encoding spells outmolecular structure from a beginning portion to an ending portion.Morgan Fingerprints may be useful for temporal molecular structures andthe descriptor module 152 may include a machine learning module trainedto output a compressed vector. Morgan Fingerprints may include theisomer for a particular molecule, and common backbone structures formolecules.

As depicted, SMILES, Morgan Fingerprints, InChl, One-Hot, N-gram,Graph-based Graphic Processing Unit Nearest Neighbor Search (GGNN), Generegulatory network (GRN), M-P Neural Network (MPNN), and Knowledge Graph(Structural/Semantic) encodings represent structural information ofmolecules (drug compounds). The Morgan Fingerprints, GGNN, GRN, and MPNNare also compressed to improve computations, while the SMILES, InChl,One-Hot, N-gram, and the Knowledge Graph are not compressed.

Quantitative structure-activity relationship (QSAR), Z-descriptors, andthe Knowledge Graph encodings may represent physiochemical properties ofmolecules. These encodings may not be compressed. The QSAR encoding mayinclude the type of activity (e.g., and without limitation to aparticular physiological or anatomical organ, organ, state or states, orto a particular disease-process, antiviral, antimicrobial, antifungal,antiemetic, antineoplastic, anti-inflammatory, leukotriene inhibitory,neurotransmitter inhibitory, etc.) the molecule provides. The encodingsselected for each type of information may optimize the computations whenconsidering such a large design space with information pertaining tostructure, physiochemical properties, and semantic information. Thelarge design space referred to may include not only a string of aminoacid sequences, and physiochemical properties, but also the semanticinformation, such as system biology and ontological information,including relationships between nodes, molecular pathways, molecularinteractions, molecular family, and the like.

FIG. 1H illustrates an example of concatenating (merging) numerousencodings into a candidate drug compound according to certainembodiments of this disclosure. A concatenated vector 191 may representan embedding for a candidate drug compound. In some embodiments, anensemble learning approach may be implemented by using different typesof techniques to generate unique encodings and merge those uniqueencodings to improve generated candidate drug compounds. As depicted,various encoding techniques may be used to represent different types ofinformation. The different types of information (e.g., structural,semantic, etc.) may be represented by unique encodings. For example,molecular graphs and Morgan Fingerprints may represent structural andphysical molecular information. Activity data (e.g., QSAR) may representmolecular structural knowledge or molecular physiochemical knowledge,and a knowledge graph may represent molecular semantic knowledge. Anattention message passing neural network (AMPNN) or long short-termmemory (LSTM) may receive the molecular graph and Morgan Fingerprints asinput and output the structural/physical information represented by 1 sand 0 s. One-hot may receive the activity data as input and output thestructural knowledge represented by is and Os. AMPNN may receive aknowledge graph as input and output semantic knowledge represented by isand Os. The resulting concatenated vector 191 is a combination of eachtype of information for a single candidate drug compound. Accordingly,the single candidate drug compound may include better properties andmore robust information than conventional techniques.

FIG. 1I illustrates an example of using a variational autoencoder (VAE)to generate a Latent Representation 168 of a candidate drug compoundaccording to certain embodiments of this disclosure. The concatenatedvector 191 (e.g., embedding) may be higher-dimensional prior to beinginput to the VAE. The VAE may be trained to translate thehigher-dimensional concatenated vector 191 to a lower-dimensionalconcatenated vector that represents the Latent Representation 168.

FIG. 2 illustrates a data structure storing a biological contextrepresentation 200 according to certain embodiments of this disclosure.Biology is context-dependent and dynamic. For example, the same moleculecan manifest multiple, potentially competing, phenotypes. Further, dataon an existing drug labeled as antimicrobial can suggest a null behaviorin applications against different microbes or even against the samemicrobes but in different contexts, e.g., temperature, pressure,environmental, contextual, comorbid. To accurately predict candidatedrug compounds that provide desirable activity levels in design spaces,the machine learning models 132 are trained to handle evolving knowledgemaps of biology and drug compounds. Further, conventional techniques fordiscovery and generating drug compounds may be ineffective forbiological data because such data is non-Euclidian.

In some embodiments, the biological context representation 200 generatedby the disclosed techniques may be used to graphically model thecontinually or continuously modifying biological and drug compoundknowledge. That is, the biology may be represented as graphs within acomprehensive knowledge graph (e.g., biological context representation200), where the graphs have complex relationships and interdependenciesbetween nodes.

The biological context representation 200 may be stored in a first datastructure having a first format. The first format may be a graph, anarray, a linked list, or any suitable data format capable of storing thebiological context representation. In particular, FIG. 2 illustratesvarious types of data received from various sources, including physicalproperties data 202, peptide activity data 204, microbe data 206,antimicrobial compound data 208, clinical outcome data 210,evidence-based guidelines 212, disease association data 214, pathwaydata 216, compound data 218, gene interaction data 220,anti-neurodegenerative compound data 222, or pro-neuroplasticitycompound data 224.

These example data may be curated by the AI engine 140 or a personhaving a certain degree (e.g., a degree in data science, molecularbiology, microbiology, etc.), certification, license (e.g., a licensedmedical doctor (e.g., M.D. or D.O.), or credential. Further, the data inthe biological context representation 200 may be retrieved from anysuitable data source (e.g., digital libraries, websites, databases,files, or the like). These examples are not meant to be limiting. Thus,the example types of data are also not meant to be limiting and othertypes of data may be stored within the biological context representationwithout departing from the scope of this disclosure. Further, thevarious data included in the biological context representation 200 maybe linked based on one or more relationships between or among the data,in order to represent knowledge pertaining to the biological context ordrug compound.

The physical properties data 202 includes physical properties exhibitedby the drug compound. The physical properties may refer tocharacteristics that provide a physical description of the drug such ascolor, particle size, crystalline structure, melting point, andsolubility. In some instances, the physical properties data 202 may alsoinclude chemical property data, such as the structure, form, andreactivity of a substance. In some embodiments, biological data may alsobe included (e.g., anti-neurodegenerative compound data,pro-neuroplasticity compound data, anti-cancer data) in the biologicalcontext representation 200.

The peptide activity data 204 may include various types of activityexhibited by the drug. For example, the activity may be hormonal,antimicrobial, immunomodulatory, cytotoxic, neurological, and the like.A peptide may refer to a short chain of amino acids linked by peptidebonds.

The microbe data 206 may include information pertaining to cellularstructure (e.g., unicellular, multicellular, etc.) of a microscopicorganism. The microbes may refer to bacteria, parasites, fungi, viruses,prions, or any combination of these, etc.

The antimicrobial compound data 208 may include information pertainingto agents that kill microbes or stop their growth. This data may includeclassifications based on the microorganisms against which theantimicrobial compound acts (e.g., antibiotics act against bacteria butnot against viruses; antivirals act against viruses but not againstbacteria). The antimicrobial compound may also be classified accordingto function (e.g., microbicidal, meaning “that which kills, vitiates,inactivates or otherwise impairs the activity of certain microbes”).

The clinical outcome data 210 may include information pertaining to theadministration of a drug compound to a subject in a clinical setting.For example, upon or subsequent to administration of the drug compound,the outcome may be a prevented disease, cured disease, treated symptom,etc.

The evidence-based guidelines 212 may include information pertaining toguidelines based upon clinical studies for acceptable treatment ortherapeutics for certain diseases or medical conditions. Evidence-basedguidelines data 212 may include data specific to various specialtieswithin healthcare such as, for example, obstetrics, anesthesiology,hepatology, gastroenterology, neurology, pulmonology, orthopedics,pediatrics, trauma care (including but not limited to burns andpost-burn infections), histology, oncology, ophthalmology,endocrinology, rheumatology, internal medicine, surgery (includingreconstructive (plastic) and cosmetic), vascular medicine, emergencymedicine, radiology, psychiatry, cardiology, urology, gynecology,genetics, and dermatology. In the example described herein, theevidence-based guidelines 212 include systematically developedstatements to assist practitioner and patient decisions aboutappropriate health care (e.g., types of drugs to prescribe fortreatment) for specific clinical circumstances.

The disease association data 214 may include information about whichdisease or medical condition the drug compounds are associated with. Forexample, the drug compound Metformin may be associated with the diseasetype 2 diabetes.

The pathway data 216 may include information pertaining in a designspace to the relationships or paths between ingredients (e.g.,chemicals) and activity levels.

The compound data 218 may include information pertaining to the compoundsuch as the sequence of ingredients (e.g., type, amount, etc.) in thecompound. In the therapeutics industry, for example, the compound data218 can include data specific to the various types of drug compoundsthat are designed, defined, developed, or distributed.

The gene interaction data 220 may include information pertaining towhich gene the drug compound or a disease may interact with.

The anti-neurodegenerative compound data 222 may include informationpertaining to characteristics of anti-neurodegenerative compounds, suchas their physical and chemical properties and activities on portions oftissue. For example, the activity may include anti-inflammatory orneuro-protective actions.

The pro-neuroplasticity compound data 224 may include informationpertaining to characteristics of pro-neuroplasticity compound, such astheir physical and chemical properties and activities on portions oftissue. For example, the activity may enhance the capacity of motorsystems by upregulation of neurotrophins.

FIGS. 3A-3B illustrate a high-level flow diagram according to certainembodiments of this disclosure. Regarding FIG. 3A, a flow diagram 300begins with obtaining heterogeneous datasets, such as the biologicalcontext representation 200. Heterogeneous datasets may refer topopulations or samples of data that are different (e.g., as opposed tohomogenous datasets where the data is the same). The heterogeneousdatasets may include compound data (e.g., peptide sequence data),clinical outcome data, or activity data (in vitro and in vivo activity),as well as any other suitable data depicted in FIG. 2.

The data structure storing the heterogeneous datasets may be translatedto a second data structure having a second format (e.g., a 2-dimensionalvector) that the AI engine 140 may use to generate the candidate drugcompounds. The next step in the flow diagram 300 includes training theone or more machine learning models 132 using the heterogeneousdatasets. The one or more machine learning models 132 (e.g., generativemodels) may generate a set of candidate drug compounds based on theheterogeneous datasets. As described herein, a machine learning modelmay use causal inference and counterfactuals when generating the set ofcandidate drug compounds. Further, a GAN may be used in conjunction withcausal inference to generate the set of candidate drug compounds. Insome embodiments, a certain number (e.g., over 100,000 candidate drugcompounds) of novel candidate drug compounds may be generated in a set.That is, each candidate drug compound in the set of candidate drugcompounds is intended to be unique.

The next step in the flow diagram 300 includes inputting the set ofcandidate drug compounds into one or more machine learning models 132trained to classify the set of candidate drug compounds. The machinelearning models 132 may perform supervised or unsupervised filtering. Insome embodiments, the machine learning models 132 may perform clusteringto rank the various candidate drug compounds to classify one candidatedrug compound as a selected candidate drug compound. In someembodiments, the machine learning models 132 may output a subset (e.g.,1,000 to 10,000, or more, or fewer) of candidate drug compounds.

The next step in the flow diagram 300 may include performingexperimental validation by validating whether each candidate drugcompound in the subset of candidate drug compounds provides the desiredlevel of certain types of activity in a design space. The results of theexperimental validation may be fed back into the heterogeneous datasetto reinforce and expand the experimental dataset.

The next step in the flow diagram 300 may include performing peptidedrug optimization. The optimizations may include performing gradientdescent or ascent using the sequence of ingredients in the candidatedrug compounds to attempt to increase or decrease certain activitylevels in a design space. The results of the peptide drug optimizationmay be fed back into the heterogeneous datasets to reinforce and expandthe experimental dataset.

FIG. 3B illustrates another high-level flow diagram 310 according tosome embodiments. As depicted, a heterogeneous network of biology may beincluded in a knowledge graph of a biological context representation200. Various paths or meta-paths may be expressed between nodes in thebiological context representation 200. For example, the meta-paths mayinclude indications for compound upregulates, pathway participates,disease associations, gene interactions, and compound data.

The biological context representation 200 may be translated from a firstformat (e.g., knowledge graph) to a format (e.g., vector) that may beprocessed by the AI engine 140. The AI engine 140 may use one or moremachine learning models to traverse the knowledge graph by performingrandom walks until a corpus of random walks is generated, wherein suchrandom walks include the indications associated with the meta-pathsrepresenting sequences of ingredients. The corpus of random walks may bereferred to as a set of candidate drug compounds. A generativeadversarial network using causal inference may be used to generate theset of candidate drug compounds. The set of candidate drug compounds maybe stored in a higher-dimensional vector.

The AI engine 140 may compress the higher-dimensional vector of the setof candidate drug compounds into a lower-dimensional vector of the setof candidate drug compounds, depicted as biological embeddings in FIG.3B. In some embodiments, the lower-dimensional vector may include fewerdimensions (e.g., 2, 3, . . . N) than the higher-dimensional vector(e.g., greater than N). As depicted, the nodes may be organized by themeta-path indicators and by dimension.

To output a subset of candidate drug compounds, the lower-dimensionalvector of the set of candidate drug compounds may be input to one ormore machine learning models 132 trained to perform classification. Theclassification techniques may include using clustering to filter outcandidate drug compounds that produce undesirable levels of types ofactivity. In some embodiments, to enable the AI engine 140 to performthe classification, views presenting the levels of types of activity ofeach candidate drug compound in a design space may be generated usingthe lower-dimensional vectors. These views may also be presented to auser via the computing device 102. The machine learning models 132 mayoutput a candidate drug candidate classified as a selected candidatedrug candidate based on the clustering. For example, the selectedcandidate drug candidate may include an optimized sequence ofingredients that provides the most desirable levels of a certain type ofactivity in a design space.

FIG. 4 illustrates example operations of a method 400 for generating andclassifying a candidate drug candidate compound according to certainembodiments of this disclosure. The method 400 is performed byprocessing logic that may include hardware (circuitry, dedicated logic,etc.), software (such as is run on a general-purpose computer system ora specialized machine), or a combination of both. The method 400 or eachof their individual functions, routines, subroutines, or operations maybe performed by one or more processors of a computing device (e.g., anycomponent of FIG. 1, such as server 128 executing the artificialintelligence engine 140). In certain implementations, the method 400 maybe performed by a single processing thread. Alternatively, the method400 may be performed by two or more processing threads, each threadimplementing one or more individual functions, routines, subroutines, oroperations of the methods In some embodiments, one or more acceleratorsmay be used to increase the performance of a processing device byoffloading various functions, routines, subroutines, or operations fromthe processing device. One or more operations of the method 400 may beperformed by the training engine 130 of FIG. 1.

For simplicity of explanation, the method 400 is depicted and describedas a series of operations. However, operations in accordance with thisdisclosure can occur in various orders or concurrently, and with otheroperations not presented and described herein. For example, theoperations depicted in the method 400 may occur in combination with anyother operation of any other method disclosed herein. Furthermore, notall illustrated operations may be required to implement the method 400in accordance with the disclosed subject matter. In addition, thoseskilled in the art will understand and appreciate that the method 400could alternatively be represented as a series of interrelated statesvia a state diagram or events.

At 402, the processing device may generate a biological contextrepresentation 200 of a set of drug compounds. The biological contextrepresentation 200 may include a first data structure having a firstformat (e.g., a knowledge graph). The biological context representation200 may include, for each drug compound of the set of drug compounds,one or more relationships between or among, without limitation, (i)physical properties data 202, (ii) peptide activity data 204, (iii)microbe data 206, (iv) antimicrobial compound data 208, (v) clinicaloutcome data 210, (vi) evidence-based guidelines 212, (vii) diseaseassociation data 214, (viii) pathway data 216, (ix), compound data 218,(x) gene interaction data 220, (xi) antimicrobial compound data, (xii)pro-neuroplasticity data 224, or some combination thereof.

At 404, the processing device may translate, by the artificialintelligence engine 140, the first data structure having the firstformat to a second data structure having a second format. Thetranslating may include converting the first data structure having thefirst format (e.g., knowledge graph) to the second data structure havingthe second format (e.g., vector) according to a specific set of rulesexecuted by the artificial intelligence engine 140. In some embodiments,the translating may be performed by one or more of the machine learningmodels 132. For example, a recurrent neural network may perform at leasta portion of the translating.

The translating may include obtaining a higher-dimensional vector andcompressing the higher-dimensional vector into a lower-dimensionalvector (e.g., two-dimensional, three-dimensional, four-dimensional),referred to as an embedding herein. In some embodiments, one or moreembeddings may be created from the first data structure having the firstformat. There may be any suitable number of dimensions of theembeddings. When used for classifying candidate drug compounds, thenumber of dimensions may be selected based on a desired performance toprocess the embeddings. The lower-dimensional vector may have at leastone fewer dimension than the higher-dimensional vector.

At 406, the processing device may generate, based on the second datastructure having the second format, a set of candidate drug compounds.In some embodiments, the generating may be performed by one or more ofthe machine learning models 132. For example, a generative adversarialnetwork may perform the generating of the set of candidate drugcompounds. In some embodiments, the set of candidate drug compounds maybe associated with design spaces pertaining to antimicrobial,anticancer, antibiofilm, or the like. A biofilm may include anysyntrophic consortium of microorganisms in which cells stick to eachother and often also to a surface. These adherent cells may becomeembedded within an extracellular matrix that is composed ofextracellular polymeric substances (EPS).

At 408, the processing device may classify a candidate drug compoundfrom the set of candidate drug compounds as a selected candidate drugcompound. In some embodiments, the classifying may be performed by oneor more of the machine learning models 132. For example, a classifiertrained using supervised or unsupervised learning may perform theclassifying. In some embodiments, the classifier may use clusteringtechniques to rank and classify the selected candidate drug compound.

In some embodiments, the processing device may generate a set of viewsincluding a representation of a design space. The design space may beantimicrobial. The processing device may cause the set of views to bepresented on a computing device (e.g., computing device 102). Therepresentation of the design space may pertain to, without limitation,(i) antimicrobial activity, (ii) immunomodulatory activity, (iii)neuromodulatory activity, (iv) cytotoxic activity, or some combinationthereof. Each view of the set of views may present an optimized sequencerepresenting the selected candidate drug compound.

The optimized sequence in each view may be generated using any suitableoptimization technique. The optimization technique may includemaximizing or minimizing an objective function by systematicallyselecting input values from a domain of values and computing the valueusing the objective function. The domain of values may include a subsetof values from a Euclidean space. The subset of values may satisfy oneor more constraints, equalities, or inequalities. A value that minimizesor maximizes the objective function may be referred to as an optimalsolution. Certain values in the subset may result in a gradient of theobjective function being zero. Those certain values may be at stationarypoints, where a first derivative at those points with respect to time(dt) is zero. The gradient may refer to a scalar-valued differentiablefunction (e.g., objective function) of several variables, where a pointp is a vector whose components are the partial derivatives of theobjective function. If the gradient is not a zero vector at a certainpoint p, then a direction of the gradient is the direction of fastestincrease of the objective function at the certain point p.

Gradients may be used in gradient descent, which refers to a first-orderiterative optimization algorithm for finding the local minimum of anobjective function. To find the local minimum, gradient descent mayproceed by performing operations proportional to the negative of thegradient of the objective function at a current point. In someembodiments, the optimized sequence may be found for a candidate drugcompound performing gradient descent in the design space. Additionally,gradient ascent, which is the algorithm opposite to gradient descent,may determine a local maximum of the objective function at variouspoints in the design space.

The views generated may include a topographical heatmap, itselfincluding indicators for the least activity at points in the designspace and the most activity at points in the design space. The indicatorassociated with the most activity may represent a local maximum obtainedusing gradient ascent. The indicator associated with the least activitymay represent a local minimum obtained using gradient descent. Theoptimal sequence may be generated by navigating points between the localminima and local maxima. The optimized sequence may be overlaid on theindicators ranging from at least one least active property to an atleast one most active property.

In some embodiments, the processing device may cause the selectedcandidate drug compound to be formulated. In some embodiments, theprocessing device may cause the selected candidate drug compound to becreated, manufactured, developed, synthesized, or the like. In someembodiments, the processing device may cause the selected candidate drugcompound to be presented on a computing device (e.g., computing device102). The selected candidate drug compound may include one or moreactive ingredients (e.g., chemicals) at a specified amount.

FIGS. 5A-5D provide illustrations of generating a first data structureincluding a biological context representation 200 of a plurality of drugcompound devices according to certain embodiments of this disclosure.The first data format may include a knowledge graph. The biologicalcontext representation 200 may capture an entire biological context byintegrating every known association or relationship for each drugcompound into a comprehensive knowledge graph.

FIG. 5A presents the biological context representation 200 includingbiomedical and domain knowledge on peptide activity, microbes,antimicrobial compounds, clinical outcomes, and any relevant informationdepicted in FIG. 2. A table 500 may include rows representing variouscategories (A, B, C, D, and E) pertaining to a biological context foreach drug compound and columns representing sub-categories (1, 2, 3, 4,and 5). For example, the table includes subcategories for category A: A12D fingerprints, A2 3D fingerprints, A3 Scaffolds, A4 Structure Keys, A5Physicochemical/B: B1 Mechanism. Of activity, B2 Metabolic Genes, B3Crystals, B4 Binding, B5 High-throughput Screening bioassays/C: C1 S.molecular Roles, C2 S. molecular Pathway, C3 Signal. Pathway, C4Biological Process, C5 Interactome/D: D1

Transcript, D2 Cancer Cell lines, D3 Chromosome Genetics, D4 Morphology,D5 Cell bioassays/E: E1 Therapeutic Areas, E2 Indications, E3 Sideeffects, E4 Disease & Toxicology, E5 Drug-drug interaction.

Charts 502, 504, and 506 represent characteristics for each subcategory.The characteristics for chart 502 include the size of molecules, forchart 504 the complexity of variables, and for 506 the correlation withmechanism of action. Another chart 508 may represent the variouscharacteristics of the subcategories using an indicator (such as a rangeof colors from 0 to 1) to express the values of the characteristics inrelation to each other.

FIG. 5B illustrates a different representation 520 of characteristicsfor several subcategories (e.g., A1, B1, C5, D1, and E3) acrossdifferent subject matter areas (e.g., neurology and psychiatry,infectious disease, gastroenterology, cardiology, ophthalmology,oncology, endocrinology, pulmonary, rheumatology, and malignanthematology.). Accordingly, the representation 520 provides an even moregranular representation of the biological context representation 200than does the chart 508. Flowchart 530 represents the process forgenerating candidate drugs as described further herein.

FIG. 5C illustrates a knowledge graph 540 representing the biologicalcontext representation 200. The knowledge graph 540 may refer to acognitive map. In particular, the knowledge graph 540 represents a graphtraversed by the AI engine 140, when generating candidate drug compoundshaving desired levels of certain types of activity in a design space.Individual nodes in the knowledge graph 540 represent a health artifact(health-related information) or relationship (predicate) gleaned andcurated from numerous data sources. Further, the knowledge representedin the knowledge graph 540 may be improved over time as the machinelearning models discover new associations, correlations, orrelationships. The nodes and relationships may form logical structuresthat represent knowledge (e.g., Genes, Participates, and Pathways). FIG.5D illustrates another representation of the knowledge graph 540 thatmore clearly identifies all the various relationships among the nodes.

FIG. 6 illustrates example operations of a method 600 for translatingthe first data structure of FIGS. 5A-5B a second data structureaccording to certain embodiments of this disclosure. Method 600 includesoperations performed by processors of a computing device (e.g., anycomponent of FIG. 1, such as server 128 executing the artificialintelligence engine 140). In some embodiments, one or more operations ofthe method 600 are implemented in computer instructions that are storedon a memory device and executed by a processing device. The method 600may be performed in the same or a similar manner as described above inregard to method 400. The operations of the method 600 may be performedin some combination with any of the operations of any of the methodsdescribed herein.

The method 600 may include operation 404 from the previously describedmethod 400 depicted in FIG. 4. For example, at 404 in the method 600,the processing device may translate, by the artificial intelligenceengine 140, the first data structure having the first format (e.g.,knowledge graph) to the second data structure having the second format(e.g., vector). The method 600 in FIG. 6 includes operations 602 and604.

At 602, the processing device may obtain a higher dimensional vectorfrom the biological context representation 200. This process is furtherillustrated in FIG. 7.

At 604, the processing device may compress the higher-dimensional vectorto a lower dimensional-vector. The compressing may be performed by afirst machine learning model 132 trained to perform deep autoencodingvia a recurrent neural network configured to output thelower-dimensional vector.

At 606, the processing device may train the first machine learning model132 by using a second machine learning model 132 to recreate the firstdata structure having the first format. The second machine learningmodel 132 is trained to perform a decoding operation to recreate thefirst data structure having the first format. The decoding operation maybe performed on the second data structure having the second data format(e.g., two-dimensional vector).

FIG. 7 provides illustrations of translating the first data structure ofFIGS. 5A-5B to the second data structure according to certainembodiments of this disclosure. Aggregated biological data may bedifficult to model and format correctly for an AI engine to process.Aspects of the present disclosure overcome the hurdle of modeling andformatting the aggregated biological data to enable the AI engine 140 togenerate candidate drug compounds accurately and efficiently.

As depicted, a higher-dimensional vector 700 may be obtained from thebiological context representation 200. Using a recurrent neural networkperforming autoencoding, the higher-dimensional vector is compressed toa lower-dimensional vector 702. The recurrent neural network performingautoencoding is trained using another machine learning model 132 thatrecreates the higher-dimensional vector 704. If the other machinelearning model 132 is unable to recreate higher-dimensional vector 704from the lower-dimensional vector 702, then the other machine learningmodel 132 provides feedback to the recurrent neural network performingautoencoding in order to update its weights, biases, or any suitableparameters.

FIGS. 8A-8C provide illustrations of views of a selected candidate drugcompound according to certain embodiments of this disclosure. Asdepicted, FIG. 8A illustrates a view 800 including antimicrobialactivity, FIG. 8B illustrates a view 802 including immunomodulatoryactivity, and FIG. 8C illustrates a view 804 including cytotoxicactivity. Each view presents a topographical heatmap where one axis isfor sequence parameter y and the other axis is for sequence parameter x.Each view includes an indicator ranging from a least active property toa most active property. Further each view includes an optimized sequence806 for a selected candidate drug compound classified by the classifier(machine learning model 132). These views may be presented to the useron a computing device 102. Further, the selected candidate drug compound806 may be formulated, generated, created, manufactured, developed, ortested.

FIG. 9 illustrates example operations of a method 900 for presenting aview including a selected candidate drug compound according to certainembodiments of this disclosure. Method 900 includes operations performedby processors of a computing device (e.g., any component of FIG. 1, suchas computing device 102). In some embodiments, one or more operations ofthe method 1000 are implemented in computer instructions that are storedon a memory device and executed by a processing device. The method 1000may be performed in the same or a similar manner as described above inregard to method 400. The operations of the method 1000 may be performedin some combination with any of the operations of any of the methodsdescribed herein.

At 902, the processing device may receive, from the artificialintelligence engine 140, a candidate drug compound generated by theartificial intelligence engine 140.

At 904, the processing device may generate a view including thecandidate drug compound overlaid on a representation of a design space.The view may present a topographical heatmap of the representation ofthe design space. The topographical heatmap may include the candidatedrug compound overlaid on indicators ranging from an at least one leastactive property to an at least one most active property. Although atopographical heatmap is depicted as an example in the view, othersuitable visual elements (e.g., graphs, charts, two-dimensional densityplots, three-dimensional density plots, etc.) may be used to depict therepresentation of the design space.

At 906, the processing device may present the view on a display screenof a computing device (e.g., computing device 102).

FIG. 10A illustrates example operations of a method 1000 for usingcausal inference during the generation of candidate drug compoundsaccording to certain embodiments of this disclosure. Method 1000includes operations performed by processors of a computing device (e.g.,any component of FIG. 1, such as server 128 executing the artificialintelligence engine 140). In some embodiments, one or more operations ofthe method 1000 are implemented in computer instructions that are storedon a memory device and executed by a processing device. The method 1000may be performed in the same or a similar manner as described above inregard to method 400. The operations of the method 1000 may be performedin some combination with any of the operations of any of the methodsdescribed herein.

At 1002, the processing device may perform one or more modificationspertaining to the biological context representation 200, the second datastructure having the second format, or some combination thereof.

At 1004, the processing device may use causal inference to determinewhether the one or more modifications provide one or more desiredperformance results. In some embodiments, using causal inference mayfurther include using 1006 counterfactuals to calculate alternativescenarios based on past actions, occurrences, results, regressions,regression analyses, correlations, or some combination thereof. Acounterfactual may refer to determining whether the desired performancestill results if something does not occur during the calculation. Forexample, in a scenario, a person may improve their health after taking amedication. The counterfactual may be used in causal inference tocalculate an alternative scenario to see whether the person's healthimproved without taking the medication. If the person's health stillimproved without taking the medication it may be inferred that themedication did not cause the health of the person to improve. However,if the person's health did not improve without taking the medication, itmay be inferred that the medication is correlated with causing thehealth of the person to improve. There may, however, be other factorsinvolved in conjunction with taking the medication that actually causethe health of the person to improve.

FIG. 10B illustrates another example of operations of method 1050 forusing causal inference during the generation of candidate drug compoundsaccording to certain embodiments of this disclosure. Method 1050includes operations performed by processors of a computing device (e.g.,any component of FIG. 1, such as server 128 executing the artificialintelligence engine 140). In some embodiments, one or more operations ofthe method 1050 are implemented in computer instructions that are storedon a memory device and executed by a processing device. The method 1050may be performed in the same or a similar manner as described above inregard to method 400. The operations of the method 1050 may be performedin some combination with any of the operations of any of the methodsdescribed herein.

At 1052, the processing device may generate a set of candidate drugcompounds by performing a modification using causal inference based on acounterfactual. For example, the counterfactual may include removing aningredient from a sequence of ingredients to determine whether acandidate drug compound provides the same level or type of activity itpreviously provided when the ingredient was included in the sequence. Ifthe same level or type of activity is still provided after applicationof the counterfactual (e.g., removal of the ingredient), then theprocessing device may use causal inference to determine that theingredient is not correlated with the level or type of activity. If thesame level or type of activity is not present after application of thecounterfactual (e.g., removal of the ingredient), then the processingdevice may use causal inference to determine that the ingredient iscorrelated with the level or type of activity.

At 1054, the processing device may classify a candidate dug compoundfrom the set of candidate drug compounds as a selected candidate drugcompound, as previously described herein.

FIG. 11 illustrates example operations of a method 1100 for usingseveral machine learning models in an artificial intelligence enginearchitecture to generate peptides according to certain embodiments ofthis disclosure. Method 1100 includes operations performed by processorsof a computing device (e.g., any component of FIG. 1, such as server 128executing the artificial intelligence engine 140). In some embodiments,one or more operations of the method 1100 are implemented in computerinstructions stored on a memory device and executed by a processingdevice. The method 1100 may be performed in the same or a similar manneras described above in regard to method 400. The operations of the method1100 may be performed in some combination with any of the operations ofany of the methods described herein.

At block 1102, the processing device may generate, via a creator module151, a candidate drug compound including a sequence for candidate drugcompound. The sequence for the candidate drug compound includes aconcatenated vector that may include drug compound sequence information,drug compound activity information, drug compound structure information,and drug compound semantic information.

In some embodiments, the candidate drug compound may be generated usinga GAN. In some embodiments, the processing device may use an attentionmessage passing neural network including an attention mechanism thatidentifies and assigns a weight to a desired feature in a portion of theknowledge graph. The desired feature may be included in the candidatedrug compound as drug compound semantic information, drug compoundstructural information, drug compound activity information, or somecombination thereof.

In some embodiments, the creator module 151 may generate the candidatedrug compound by performing ensemble learning by concatenating a set ofencodings. The encodings may each respective sequences represented in avector. A first encoding of the set of encodings may pertain to drugcompound sequence information. A second encoding of the set of encodingsmay pertain to drug compound structural information. A third encoding ofthe set of encodings may pertain to peptide activity information. Afourth encoding of the set of encodings may pertain to drug compoundsemantic information.

In some embodiments, the creator module 151 may generate the candidatedrug compound using an autoencoder machine learning model trained toreceive a higher-dimensional vector encoding representing the candidatedrug compound and output a lower-dimensional vector embeddingrepresenting the candidate drug compound. The creator module 151 maygenerate a latent representation using the lower-dimensional vectorembedding representing the candidate drug compound.

At block 1104, the processing device may include, via the creator module151, the candidate for the candidate drug compound as a node in aknowledge graph (e.g., biological context representation 200). In someembodiments, the knowledge graph may include a first layer includingstructure and physical properties of molecules, a second layer includingmolecule-to-molecule interactions, a third layer including molecularpathway interactions, a fourth layer including molecular cell profileassociations, and a fifth layer including molecular therapeutics andindications. Indications may refer to drug indications, or the diseasewhich gives a valid reason for clinicians to administer a specific drug.

At block 1106, the processing device may generate, via a descriptormodule 152, a description of the candidate drug compound at the node inthe knowledge graph. The description may include drug compound sequenceinformation, drug compound structural information, drug compoundactivity information, and drug compound semantic information.

At block 1108, based on the description, the processing device mayperform, via a scientist module 153, a benchmark analysis of a parameterof the creator module 151. In some embodiments, the scientist module 153may perform causal inference using the candidate drug compound in adesign space pertaining to biomedical activity (e.g., antimicrobial,anticancer, etc.) to determine if the candidate drug compound stillprovides a desired effect regarding the type of biomedical activity ifthe candidate drug compound, or the design space, is changed.

At block 1110, the processing device may modify, based on the benchmarkanalysis, the creator module 151 to change the parameter in a desiredway during a subsequent benchmark analysis. Changing the parameter in adesired way may refer to changing a value of the parameter in a desiredway. Changing the value of the parameter in the desired way may refer toincreasing or decreasing the value of the parameter. Accordingly, aself-improving AI engine 140 is disclosed that increasingly generatesbetter candidate drug components over time by recursively updating thecreator module 151 based on baselines. In some embodiments, “change theparameter” means change a value of the parameter as desired (e.g.,either increase or decrease).

In some embodiments, the processing device may generate, via areinforcer module 154 based on the candidate drug compound and thedescription, experiments that produce desired data for the candidatedrug compound. The experiments may be generated in response to thecandidate drug compound and the description being similar to a real drugcompound and another description of the real drug compound. For example,the reinforce module 154 may determine that certain experiments for thereal drug compound elicited desired data and may select thoseexperiments to perform for the candidate drug compound. The processingdevice may perform the experiments (e.g., by running simulations) tocollect data pertaining to the candidate drug compound. The processingdevice may determine, based on the data, an effectiveness of thecandidate drug compound.

FIG. 12 illustrates example operations of a method 1200 for performing abenchmark analysis according to certain embodiments of this disclosure.Method 1200 includes operations performed by processors of a computingdevice (e.g., any component of FIG. 1, such as server 128 executing theartificial intelligence engine 140). In some embodiments, one or moreoperations of the method 1200 are implemented in computer instructionsthat are stored on a memory device and executed by a processing device.The method 1200 may be performed in the same or a similar manner asdescribed above in regard to method 400. The operations of the method1200 may be performed in some combination with any of the operations ofany of the methods described herein.

The method 1200 includes additional operations included in block 1108 ofFIG. 11. At block 1202, the processing device generates, via thescientist module 143, a score for a parameter of the creator module 151that generated the candidate drug compound. The parameter may include avalidity of the candidate drug compound, uniqueness of the candidatedrug compound, novelty of the candidate drug compound, similarity of thecandidate drug compound to another candidate drug compound, or somecombination thereof.

At block 1204, the processing device may rank a set of creator modules151 based on the score, where the set of creator modules comprises thecreator module. For example, other creator modules in the set of creatormodules may be scored based on the candidate drug compounds theygenerated. The set of creator modules may be ranked for each respectivecategory from highest scoring to lowest scoring or vice versa.

At block 1206, the processing device may determine which creator module151 of the set of creator modules performs better for each respectiveparameter. The scores of the parameters for each of the set of creatormodules 151 may be presented on a display screen of a computing device.The best performing creator modules for each parameter may also bepresented on the display screen.

At block 1208, the processing device may tune the set of creator modules151 to cause the set of creator modules 151 to receive higher scores forcertain parameters during subsequent benchmark analysis. The tuning mayoptimize certain weights, activation functions, hidden layer number,loss, and the like of one or more generative modules included in thecreator modules.

At block 1210, the processing device may select, based on theparameters, a subset of the set of creator modules 151 to use togenerate subsequent candidate drug compounds having desired parameterscores. For example, it may be desired to generate drug candidatecompounds that result in a high uniqueness score. The creator module(s)151 associated with high uniqueness scores may be selected in the subsetof creator modules 151.

At block 1212, the processing device may transmit the subset of the setof creator modules as a package to a third-party to be used with data ofthe third-party. The subset of the set of creator modules may be trainedto process a type of the data of the third-party. Other modules, such asthe reinforce module, the descriptor module, the scientist module, andthe conductor module may be included in the package delivered to thethird-party. Also, a knowledge graph including data pertaining to thethird-party may be included in the package. In such a way, the disclosedtechniques may provide custom tailored packages that may be used by thethird party to perform the embodiments disclosed herein.

FIG. 13 illustrates example operations of a method 1300 for slicing alatent representation based on a shape of the latent representationaccording to certain embodiments of this disclosure. Method 1300includes operations performed by processors of a computing device (e.g.,any component of FIG. 1, such as server 128 executing the artificialintelligence engine 140). In some embodiments, one or more operations ofthe method 1300 are implemented in computer instructions stored on amemory device and executed by a processing device. The method 1300 maybe performed in the same or a similar manner as described above inregard to method 400. The operations of the method 1300 may be performedin some combination with any of the operations of any of the methodsdescribed herein.

At block 1302, the processing device may determine a shape of themulti-dimensional, continuous representation of the set of candidates.At block 1304, the processing device may determine, based on the shape,a slice to obtain from the multi-dimensional, multi-dimensional,continuous representation of the set of candidates. At block 1306, theprocessing device may determine, using a decoder, which dimensions areincluded in the slice. The dimensions may pertain to peptide sequenceinformation, peptide structural information, peptide activityinformation, peptide semantic information, or some combination thereof.At block 1308, the processing device may determine, based on thedimensions, an effectiveness of a biomedical feature of the slice.

FIG. 14 illustrates a high-level flow diagram for a therapeutics toolimplementing, incorporating or using business intelligence according tocertain embodiments of this disclosure. A business intelligence screenmay be presented in a graphical user interface on the computing device102. The computing device 102 may be operated by a person assigned to adevelopment team, business intelligence team, or the like. The userinterface may include various graphical elements (e.g., buttons, sliderbars, radio buttons, input boxes, etc.) that enable the user to enter,select, configure, etc. a desired target product profile 1400 forsequences (e.g., peptide). The target product profile may includepharmacology data 1402 (e.g., drug brand name (if applicable), druggeneric name, drug dose, clinical trial information and results,toxicology, stability, safety, efficacy, dose cost, etc.),pharmacokinetic data, pharmacodynamic data, activity data, manufacturingdata 1404 (e.g., liquid chromatography mass spectrometry (LCMS) data,ability to be manufactured, scalability in production, etc.), compliancedata, biological data 1406 (e.g., metabolic information (e.g.,half-life, LD50, etc.), sequence data, pathway, interactions,indications, symptoms, genes, etc.), or some combination thereof. Insome embodiments, while the user interface is presenting a design spacefor proteins, the target product profile may be entered, selected,configured, etc. via the user interface. The computing device 102 or theartificial intelligence engine 140 may select or filter the design spaceto present a solution space which includes sequences that match (e.g.,partially or exactly) the target product profile.

The sequences may be selected, based on the target product profile, froma library of sequences. The library of sequences may be generated by oneor more machine learning models 132 of the artificial intelligenceengine 140 performing the techniques described herein. In someembodiments, if a certain number of sequences (e.g., 0, 5, 10, etc.) arefound or not found to have a matching target product profile, then theartificial intelligence engine 140 may attempt to generate sequenceshaving features pertinent to the target product profile. The dynamicallygenerated sequences may be added to the library of sequences and may bepresented on the user interface of the computing device 102.

The sequences that match the target product profile may include a listof candidate drug compounds (e.g., peptide candidates) or relevantcandidate drug compound features. The features may include biomedicalontological relations, terms, characteristics, descriptors, or the likeor non-biomedical ontological relations, terms, characteristics,descriptors, or the like. For example, the features may include levelsof structural (e.g., physical, chemical, biological, etc.) information,semantic information, activity, classes of activity, indications (e.g.,clinical outcomes), genes, indications, symptoms, interactions, foldingproperties, wave properties, stabilities of modification, sequenceinformation (e.g., location or number of amino acids in a strand), andso forth. The user may use one or more graphical elements presented onthe graphical user interface to select one or more of the sequences.Selecting the one or more sequences may cause another user interface,such as a candidate dashboard screen, to present additional datapertaining to the one or more selected sequences. In some embodiments,selecting the one or more sequences may cause the one or more sequencesto be manufactured, produced, synthesized, or the like.

FIG. 15 illustrates an example user interface 1500 for using queryparameters to generate a solution space including protein sequencesaccording to certain embodiments of this disclosure. The user interface1500 includes a first portion 1502 and a second portion 1504. The firstportion includes a landscape view of a solution space 1506 within adesign space. Various color-coded clusters may be represented thesequences included in the solution space. The sequences are visualizedas interacting with each other via connections in a network. Informationpertaining to the sequences may be stored in eigenvectors and presentedin any number of applicable dimensions.

The first portion 1502 includes various graphical elements to enable auser to select certain information, features, identifiers, queryparameters, etc. that may be used to filter, constrain, build, generate,etc. the solution space within a design space for proteins forparticular applications. The design space may include up to everyconceivable or known (e.g., facts) configuration of sequences ofproteins (e.g., peptides) in certain biochemical or biomedicalapplications (e.g., antimicrobial, anti-cancer, anti-viral, anti-fungal,anti-prion, immunomodulatory, neuromodulatory, a physiological effectcaused by a signaling peptide, etc.).

The design space may be created based on the knowledge graph thatincludes ontological data pertaining to sequences of proteins for up toevery conceivable or known configuration of sequences of proteins. Aresolution of the design space may be modified by identifying, as afirst order, features or activities pertaining to the sequences. Theterm “resolution” may refer to the process of reducing, partitioning orseparating something into its components (e.g., features or activitiespertaining to the sequences).

For example, one graphical element 1508 may include a dropdown box thatenables entering, selecting, configuring, etc. one or more queryparameters. Although a dropdown box is shown, any suitable graphicalelement may be used. The query parameters may include desirable sequenceparameters associated with features, activities, properties,biomedically-related ontological relations, terms, characteristics,descriptors, or the like or non-biomedically-related ontologicalrelations, terms, characteristics, descriptors, or the like. The queryparameters may be used in any combination to generate differentvisualizations of solution spaces having sequences. If just one queryparameter is of interest to a user (e.g., protein engineer, proteindesigner, peptide engineer, peptide designer, etc.), then aone-dimensional visualization of sequences related to that one queryparameter may be presented in the first portion 1502. If “n” (where “n”is a positive integer) query parameters are of interest to a user, thenan n-dimensional visualization of the sequences can be related to the nquery parameters. The solution spaces that are generated or presentedmay be saved in the database 150. The artificial intelligence engine 140may distill, based on the selected query parameters, the design spaceinto the solution space 1506. For example, the distillation process mayinclude selecting sequences as candidate drug compounds that produceactivities (e.g., query parameters) exceeding a certain threshold level.The solution space 1506 may be generated to include those candidate drugcompounds.

The user interface 1500 enables a user to modify the query parameters toessentially tune the solution space presented such that desiredsequences having particular features pertaining to the query parametersare depicted at least one of efficiently, accurately, and in a condensedvisual format. Such a technique is beneficial because it distills alarge (typically, very large) amount of data in the knowledge graph downinto a visually comprehensible format, thereby increasing explainability and understandability. Due to the improved user interface 1500,a user's experience using the computing device may be enhanced becausethe user does not have to switch between or among multiple userinterfaces or to perform multiple queries to find different solutionspaces. The enhanced user interface 1500 may save computing resources byusing the query parameters to enable data reduction from a large proteindesign space to salient sequences in the solution space 1506. Further,the disclosed machine learning models may be trained to generate results(e.g., solution space 1506) superior to those results produced byconventional techniques. Additionally, the results produced using thedisclosed techniques may have been previously computationally infeasibleusing conventional techniques.

The second portion 1504 may include more granularly detailed datapertaining to the solution space 1506 and the sequences includedtherein. For example, the second portion 1504 includes a legend andvarious windows pertaining to interactions, associations, and proteins.The legend includes information pertaining to polo-box domain (e.g., thePDZ domain, SH3 domain, WW domain, WH1 domain, TK domain, PTP domain,PTB domain, SH2 domain, etc.), binding site (e.g., C-terminus,polyproline, phosphosite, etc.), interaction information, and networkinformation. The various information is color-coded and correlated withthe color-coded clusters presented in the first portion. Additionally,some of the information (e.g., polo-box domain and binding sites) in thelegend are associated with different shapes to differentiate each typeof information's graphics. The interaction information in the legenddepicts how the various selections of polo-box domain informationinteract with each other, and the network information in the legenddepicts how various clusters are connected in a network. Depicting thesolution space using these techniques may provide an enhanced userinterface by distilling a large amount of complex biochemicalinformation about candidate drug compounds into a format easilyunderstandable to a target user (e.g., peptide designer, businessintelligence user). To make decisions pertaining to selecting candidatedrug compounds without drilling down into additional screens, the usermay view the user interface 1500, thereby saving computing resources andenhancing the user's experience using the computing device 102. Thewindow, including interactions, depicts a likelihood of pairwiseinteractions between two proteins. For example, “Protein 1” Q8IXW0 and“Protein 2” Q96RU3 have a probability of 0.52 of interacting. Thewindow, including associations, includes certain information pertainingto ontological terms concerning biological functions in subgraphsassociated with the query that caused the solution space to begenerated. The window, including protein information, includes variousgraphical elements (e.g., input boxes) to enable the entering ofinformation pertaining to descriptions of the protein or ontologicalterms related to the protein.

The user interface 1500 may include one or more graphical elements 1512configured to enable selecting one or more of the sequences in thesolution space. The user may use the graphical element 1512 to select asequence to view additional information pertaining to the selectedsequence, to cause the selected sequence to be manufactured, produced,synthesized, etc. For example, if a sequence selected is in the solutionspace, a user may be shown the topographical heatmap depicted in FIGS.8A-8C. The sequence 806 depicted in FIG. 8A has a particular path alonga traversal or feature map, where the path is specific to the queryparameter entered (e.g., number of alanine amino acids). Each point onthe traversal may be associated with a particular level of activitymeasured by one or more trained machine learning models 132 thatgenerate the sequence 806. In some embodiments, selecting a sequence inthe solution space 1506 may cause another user interface 1800 to bepresented, such as a candidate dashboard screen in FIG. 18.

FIG. 16 illustrates an example user interface 1600 for trackinginformation pertaining to trials according to certain embodiments ofthis disclosure. The trial information includes columns for a name ofthe trial (computation run), a tag indicating whether the trial is atest only, a creation date (start time of execution), a runtime length,a sweep, an encoder identifier (architecture of machine learning model),a number of training data, a number of validation data, an accuracy, anepoch, a human_iou (human intersection over union), and an iou(intersection over union). Further, a feature classification metric mayalso be user defined. A feature may refer to a descriptor that a machinelearning model 132 is learning to classify. For example, one suchfeature may be “stability” and a machine learning model 132 may classifythe following: if a peptide sequence is a stable sequence. The featureclassification metric would be “stability” in that example. Othermetrics may include accuracy, precision, intersection over union, or thelike. The trial information may be useful to a protein designer byenabling the protein designer to determine which trials are moresuccessful than other trials, more accurate than other trials, and thelike. Further, the trial information may enable the protein designer togenerate new trials that include beneficial features of previous trials.

FIG. 17 illustrates an example user interface 1700 for presentingperformance metrics of machine learning models that perform trialsaccording to certain embodiments of this disclosure. As depicted, theperformance metrics may include process graphic processing unit (GPU)usage (%), process GPU power usage (%), process GPU memory allocated(%), process GPU time spent accessing memory (%), and process GPUtemperature (degrees, e.g., Celsius. Each metric may include a graphthat includes representations (e.g., lines) associated with respectivemachine learning models. The graph may include an X axis correspondingto the time or time elapsed or other time measure, and a Y axiscorresponding to a value amount (e.g., a cost value). Therepresentations for each machine learning model may be overlaid on thegraph to enable a comparison of how each machine learning modelperformed for a particular metric.

The performance metrics may be used to assign a cost value to each ofthe machine learning models. The cost may refer to how many resources(processor, memory, network, etc.) are used by the machine learningmodel during performance of trials, temperatures of components caused bythe machine learning model during performance of trials, energyutilization, memory utilization, processor utilization, and other directand indirect measures of money and non-money cost, among others.Assigning a cost (e.g., a weighted value or average as the sum of nodestraversed on a graph or as the expected value or other mathematical orstatistical measure related to such cost) to each of the machinelearning models may enable generating sequences that traverse thesolution space to a desired location in the cheapest way possible.Accordingly, the disclosed techniques may enable saving computingresources by evaluating and assigning costs to certain machine learningmodels that perform better than other machine learning models.

FIG. 18 illustrates an example user interface 1800 for a candidatedashboard screen according to certain embodiments of this disclosure.The candidate dashboard screen includes selected information (e.g.,chemical, physical, structural, chemical, semantic, etc.) about acandidate drug compound and, preferably, all of the availableinformation thereabout. The user interface 1800 may enable a user to seea snapshot of all data (e.g., structure, correlation heatmap, relatedtrials, trial result data, external references (aliases, synonyms,etc.)) related to a particular candidate drug compound. The userinterface 1800 may be presented when a user selects a sequence in thesolution space 1506 presented in FIG. 15.

The user interface 1800 includes two-dimensional 1804 andthree-dimensional 1802 energy correlations. The energy correlations maycorrespond to energy functions associated with each position in adomain. A given energy correlation represents a correlation between eachposition of a protein in relation to all the other positions in theprotein. The energy correlation may represent indications (e.g., colorcoded sections) pertaining to stability as the stability affects aspecific function. An amino acid in context with the adjacent aminoacids may affect the local folding properties of the peptide. Energycorrelation values are inversely related (although the degree ofrelation may vary) to the strength of a specific amino acid (or aminoacid modification) at a specific position in a peptide chain for apeptide designed for a specific function.

FIG. 19 illustrates example operations of a method 1900 for generating adesign space for a peptide for an application according to certainembodiments of this disclosure. Method 1900 includes operationsperformed by processors of a computing device (e.g., any component ofFIG. 1, such as computing device 102, server 128 executing theartificial intelligence engine 140, etc.). In some embodiments, one ormore operations of the method 1900 are implemented in computerinstructions stored on a memory device and executed by a processingdevice. The method 1900 may be performed in the same or a similar manneras described above in regard to method 400. The operations of the method1900 may be performed in some combination with any of the operations ofany of the methods described herein.

At block 1902, the processing device may generate a design space for apeptide for an application. The application may include at least one ofthe following functional biomaterials (e.g., adhesives, sealants,binders, chelates, diagnostic reporters, or some combination thereof)and structural biomaterials (e.g., biopolymers, encapsulation films,flocculants, desiccants, or some combination thereof): anti-infective,anti-cancer, antimicrobial, antiviral, anti-fungal, anti-inflammatory,anti-cholinergic, anti-dopaminergic, anti-serotonergic,anti-noradrenergic, anti-prionic, and anti-fungal. The processing devicemay generate the design space by (i) identifying 1904 a set of sequencesfor the peptide, and (ii) updating 1906, the set of sequences, bydetermining, for each of the set of sequences, a respective set ofactivities (e.g., immunomodulatory activity, receptor binding activity,self-aggregation, cell-penetrating activity, anti-viral activity,peptidergic activity, cell-permeating, or the like) pertaining to theapplication. Updating the set of sequences may produce an updated set ofsequences, wherein each updated set of sequences has an updatedrespective set of activities.

At block 1908, the processing device may generate, based on the updatedset of sequences each having the updated respective set of activities, asolution space within the design space. The solution space may include atarget subset of the updated set of sequences, wherein each updated setof sequences has the updated respective set of activities.

In some embodiments, the processing device may receive a query parameterselected, generated, or transmitted from a user interface presented onthe computing device 102. The processing device may use the queryparameter to generate the solution space. For example, using a machinelearning model trained to measure, based on the query parameter, a levelof the updated respective set of activities, the processing device maygenerate the solution space within the design space. One or more queryparameters may be selected as constraints to be used to generate thesolution space. Essentially, the query parameters may be used to createbounds of the solution space within the design space. The queryparameters may be selected, generated, or transmitted from a userinterface presented on the computing device 102 and transmitted to theartificial intelligence engine 140. Based on the query parameters, theartificial intelligence engine 140 may use one or more machine learningmodels to generate the solution space within the design space.

The query parameter may include sequence parameters pertaining tobiomedically-related ontological relations, terms, characteristics,descriptors, or the like or non-biomedically-related ontologicalrelations, terms, characteristics, descriptors, or the like. Forexample, the biomedical ontology terms may include indications, genes,symptoms, alanine properties, etc. The non-biomedical ontology terms mayinclude physical descriptors and characteristics, such as interactions(e.g., adhesive), folding properties (e.g., aggregating versus loose),wave properties (e.g., fluorescent, luminescent, iridescent), stabilityof modification (e.g., glycopeptides, lipid peptides, chelates, lassopeptides), etc.

In some embodiments, in addition to the query parameter, the processingdevice may receive a desired threshold level of a target activity forthe query parameter, with such threshold level configured such that thetarget subset of sequences must exceed the threshold level in order tobe included in the solution space. The desired threshold level may beany suitable value, percentage, measurement, quantity, etc. For example,a user may select a number of alanines (e.g., 5) as the query parameterand specify the desired threshold level of a target activity (e.g.,immunomodulatory activity). Accordingly, the processing device mayreturn a target subset of sequences having 5 alanines that exceed thedesired threshold level of immunomodulatory activity.

In some embodiments, the processing device may perform dimensionreduction to identify the target subset. Said reduction may be performedvia a machine learning model using the query parameter and the updatedset of sequences, using an algorithm such as uniform manifoldapproximation and projection (UMAP). UMAP, a nonlinear dimensionalityreduction technique, may scale well on sparse data. A UMAP-basedtechnique may use a Riemannian manifold, which refers to a real, smoothmanifold M equipped with a positive-definite inner product g_(p) on thetangent space T_(p)M at each point p. The family g_(p) of inner productsis called a Riemannian metric. A Riemannian metric enables definingseveral geometric notions on the Riemannian manifold, such as an angleat an intersection, length of a curve, area of a surface andhigher-dimensional analogues (e.g., volume, etc.), extrinsic curvatureof sub-manifolds, and intrinsic curvature of the manifold itself. UMAPmay assume that data is uniformly distributed on a locally connectedRiemannian manifold and that the Riemannian metric is locally constantor approximately locally constant.

The UMAP-based technique may involve certain initial assumptions suchas: (i) there exists a manifold on which the data (e.g., candidate drugcompounds) would be uniformly distributed; (ii) the underlying manifoldof interest is locally connected; or (iii) preserving the topologicalstructure of this manifold is the primary goal. Based on theassumptions, the UMAP-based technique may construct a graph by: (i)constructing a weighted k-neighbor graph; (ii) applying some transformon the edges to local distances; and (iii) dealing with the inherentasymmetry of the k-neighbor graph. The UMAP-based technique may performgraph layout procedures including: (i) defining an objective functionthat preserves desired characteristics of this k-neighbor graph; and(ii) finding a low-dimensional representation which optimizes thisobjective function.

In some embodiments, one or more other techniques may be used, such aslinear decomposition, principal component analysis (PCA), kernel PCA,matrix factorization, generalized discriminant analysis, lineardiscriminant analysis, autoencoding, or some combination thereof.

In some embodiments, the processing device may receive a selection of asequence from the target subset of sequences in the solution space. Theselection may be made using a graphical element of a user interfacepresented on the computing device 102, and the selection may betransmitted from the computing device 102 to the artificial intelligenceengine 140. In response to receiving the selection of the sequence, theprocessing device may provide information pertaining to the sequence forpresentation in a user interface on the computing device 102. Theinformation may include at least classes of proteins, protein-to-proteininteractions, protein-ligand interactions, protein homology andphylogeny, sequence and structure motifs, chemical and physicalstability measures, pharmacological associations, systems biologyattributes, protein folding descriptors or constraints, or somecombination thereof.

At block 1910, the processing device, using a machine learning model 132to process the solution space, may perform one or more trials. The oneor more trials are configured to identify a candidate drug compound thatrepresents a sequence having at least one level of activity that exceedsone or more threshold levels. The one or more threshold levels may bepredetermined or configured by a user (e.g., peptide designer). Forexample, the one or more threshold levels may be a value, percentage,amount, etc. that the candidate drug compound exhibits with respect toantiviral activity.

At block 1912, the processing device may transmit information describingthe candidate drug compound to a computing device 102. The computingdevice 102 may be operated by a drug candidate designer (e.g., protein,peptide, etc.) interested in sequences that exhibit certain activity foran application. The computing device 102 may also be operated by abusiness user interested in sequences that have certain target productprofiles (e.g., pertaining to manufacturing, pharmacology, etc.).

In some embodiments, the processing device may provide the solutionspace to the computing device 102 for presentation as a topographicalmap in a user interface of the computing device 102. The topographicalmap may include a set of indications that, for a sequence, eachrepresent a level of activity at a given point on the topographical map.FIGS. 8A-8C depict examples of topographical heatmaps that may bepresented on the user interface of the computing device 102. Asdepicted, FIG. 8A illustrates a view 800 including antimicrobialactivity, FIG. 8B illustrates a view 802 including immunomodulatoryactivity, and FIG. 8C illustrates a view 804 including cytotoxicactivity. Each view presents a topographical heatmap where one axis isfor sequence parameter y and the other axis is for sequence parameter x.Each view includes an indicator (e.g., color code) ranging from a leastactive property to a most active property. Further, each view includesan optimized sequence 806 for a selected candidate drug compoundclassified by the classifier (machine learning model 132). These viewsmay be presented to the user on a computing device 102. Further, anoptimized sequence may be selected, generated or transmitted in or viathe user interface using a graphical element (e.g., button, mousecursor, etc.). The selected sequence may cause another user interface(e.g., candidate dashboard in FIG. 18) that provides additionalinformation pertaining to the sequence to be presented. In someembodiments, selecting the sequence may cause the sequence to beformulated, generated, created, manufactured, developed, or tested.

FIG. 20 illustrates example operations of a method 2000 for comparingperformance metrics of machine learning models according to certainembodiments of this disclosure. Method 2000 includes operationsperformed by processors of a computing device (e.g., any component ofFIG. 1, such as computing device 102, server 128 executing theartificial intelligence engine 140, etc.). In some embodiments, one ormore operations of the method 2000 are implemented in computerinstructions stored on a memory device and executed by a processingdevice. The method 2000 may be performed in the same or a similar manneras described above in regard to method 400. The operations of the method2000 may be performed in some combination with any of the operations ofany of the methods described herein.

At block 2002, the processing device may determine one or more metricsof the machine learning model that performs one or more trials. The oneor more metrics may include memory usage, graphic processing unittemperature, power usage, processor usage, central processing usage, orsome combination thereof. FIG. 17 presents examples of the one or moremetrics used to analyze the machine learning model that performs the oneor more trials.

At block 2004, the processing device compares the one or more metrics toone or more second metrics of a second machine learning model thatperforms the one or more trials. The comparison may illuminate which ofthe machine learning model or the second machine learning model performsbetter than the other. For example, the machine learning model mayperform the same trials but consume less processor resources or memoryresources. Accordingly, the machine learning model may be used tosubsequently perform those trials and the second machine learning modelmay be pruned from being selected or tuned (e.g., adjusting weights,bias, levels of hidden nodes, etc.) to improve its metrics. As a result,the disclosed techniques provide a technical benefit of enabling thecontinuous or continual monitoring of the performance of the machinelearning models and, preferably, further optimizing which machinelearning models perform trials to improve metrics (e.g., processorusage, power usage, graphic processing unit temperature, etc.).

FIG. 21 illustrates example operations of a method 2100 for presenting adesign space and a solution space within a graphical user interface of atherapeutics tool according to certain embodiments of this disclosure.Method 2100 includes operations performed by processors of a computingdevice (e.g., any component of FIG. 1, such as computing device 102,server 128 executing the artificial intelligence engine 140, etc.). Insome embodiments, one or more operations of the method 2100 areimplemented in computer instructions stored on a memory device andexecuted by a processing device. The method 2100 may be performed in thesame or a similar manner as described above in regard to method 400. Theoperations of the method 2100 may be performed in some combination withany of the operations of any of the methods described herein.

At block 2102, the processing device may present, in a first screen of agraphical user interface (GUI) of a therapeutic tool, a design space fora protein for an application. In some embodiments, the therapeutic toolis a peptide therapeutic design tool, a peptide business intelligencetool, or both. In some embodiments, the protein is a peptide. The designspace may include a set of sequences each containing a respective set ofactivities pertaining to the application. As described herein, thedesign space may be generated based on a knowledge graph pertaining topeptides. The design space may be presented as a two-dimensional (2D)elevation map, a three-dimensional (3D) shape, or an n-dimensional (nD)mathematical representation.

At block 2104, the processing device may receive, via a graphicalelement (e.g., button, input box, radio button, dropdown list, slider,etc.) in the first screen, a selection of one or more query parametersof the design space. The one or more query parameters may include asequence parameter pertaining to biomedical ontology terms ornon-biomedical ontology terms. The biomedically-related ontologicalrelations, terms, characteristics, descriptors, etc. may pertain toindications, function (e.g., catalyze a chemical reaction (e.g., enzyme)or control a structure of water (antifreeze proteins)), activity (e.g.,anti-viral, anti-microbial, anti-cancer, anti-fungal, anti-prionic,etc.), genes, symptoms, or some combination thereof. Thenon-biomedically-related ontological relations, terms, characteristics,descriptors, etc. may pertain to physical characteristics, descriptors,or some combination thereof. Example physical characteristics anddescriptors may include information pertaining to interactions (e.g.,adhesive properties), folding properties, (e.g., aggregating versusloose), wave properties (e.g., fluorescent, luminescent, iridescent,etc.), measures of stability of modification (e.g., with respect toglycopeptides, lipid peptides, chelates, lasso peptides, etc.), and thelike.

At block 2106, the processing device may present, in a second screen ofthe GUI, a solution space that includes a subset of the set ofsequences, each sequence containing the respective set of activities.The subset of the set of sequences is selected based on the one or morequery parameters. In some embodiments, the solution space may begenerated within the design space by one or more machine learning models132 trained to measure, based on the one or more query parameters, arespective level of one or more of the respective set of activities ofeach of the set of sequences in the subset of sequences. The queryparameters essentially create the bounds of the solution space withinthe design space. Generating the solution space may include grouping orbinning, based on the query parameter, sequences as possible or notpossible. “Possible,” as used herein, means constructible in reality,economically feasible, chemically feasible, biologically feasible, orotherwise reasonably feasible. “Not possible,” as used herein, means notable to be constructed in reality, economically infeasible, chemicallyinfeasible, biologically infeasible, or otherwise reasonably infeasible.In some embodiments, the machine learning model 132 may be a variationalautoencoder, as described herein. In some embodiments, the machinelearning model 132 may be any suitable machine learning model capable ofperforming decomposition methods.

In some embodiments, the solution space is presented as a topographicalmap in the GUI. The topographical map may include a set of indications,wherein each set of indications represents a level of activity for asequence associated with a given point on the topographical map. In someembodiments, the second screen may include a first portion presentingone or more clusters (e.g., color-coded) representing the subset of theset of sequences. As shown in FIG. 15, the first portion may depict how,in a network, the clusters are organized and interact with each other.

In some embodiments, the one or more color-coded clusters may represent,using an energy correlation, each sequence in the subset. The energycorrelation may include a correlation between each position of eachsequence in the subset and other positions of other sequences in thesubset. The term “energy correlation” may refer to stability as itaffects a specific function of the subset of sequences, or it may alsorefer to, e.g., a strength of an amino acid in a sequence relative to astrength of another amino acid at a different position in the sequence.For example, an amino acid in context with an adjacent amino acidaffects the local folding properties of a peptide. Energy correlationvalues are, to some degree, inversely related to a strength of aspecific amino acid (or amino acid modification), where the amino acidis located at a specific position in the peptide chain.

Thus, the first portion visually represents high-level generalinformation pertaining to the set of sequences in the solution space.The visual representation of the solution space may provide an enhanceduser interface to a protein designer. For example, by visually depictingthe interactions of the clusters representing the set of sequences in anetwork, a protein designer may be provided with a vast amount ofinformation cognitively understandable by a user in a single userinterface without the user's having to view numerous user interfaces toperform additional queries as to how sequences interact with othersequences in a network.

The second screen may include a second portion presenting datapertaining to the subset of the set of sequences represented by the oneor more clusters. The data presented in the second portion may be moregranular and detailed than the data in the clusters presented in thefirst portion of the second screen. The second portion may include alegend and various windows, including detailed data, as described abovewith reference to FIG. 15. The detailed data may enable a proteindesigner to drill down to understand very specific information about theclusters presented in the solution space. The specific information maypertain to polo-box domains (PBD), binding sites, interactions, network,associations, biological functions, and the like. The detailed data maydescribe one or more objects associated with the subset of the set ofsequences. The one or more objects may include a candidate drugcompound, an activity, a drug, a gene, a pathway, a physical descriptor,an interaction (e.g., adhesive, etc.), a folding property (e.g.,aggregating versus loose), a wave property (e.g., fluorescent,luminescent, iridescent, etc.), a stability of modification (e.g.,glycopeptides, lipid peptides, chelates, lasso peptides, etc.), or somecombination thereof.

In some embodiments, the processing device may receive, using agraphical element (e.g., button, mouse cursor, input box, dropdown list,slider, radio button, etc.) of the second screen, a selection of asequence from the subset of the set of sequences. The selection may bebased on the sequence being previously untraversed. To that end, theprocessing device may store each sequence included in the subsetpresented in the solution space and may track whether the sequence hasbeen generated or traversed before. The processing device may store anindicator (e.g., flag) with each sequence in the database 150, and theindicator may represent whether the respective sequence has beentraversed or is or remains untraversed. In some embodiments, thesequence traversed may be presented in a first manner (e.g., with aparticular color) while the sequence untraversed may be presented in asecond manner (e.g., with a different color than the first manner). Insome embodiments, the second screen may provide a graphical element thatenables filtering to view only the sequences traversed or,alternatively, untraversed. Responsive to the selection of the sequence,the processing device may present, in the second screen, additionalinformation pertaining to the sequence. The additional information mayinclude a candidate drug compound, an interaction, an activity, a drug,a gene, a pathway, or some combination thereof.

In some embodiments, the processing device may receive, using agraphical element of the second screen, a selection of a sequence fromthe subset of the set of sequences. The processing device may present,in a third screen, a candidate dashboard (e.g., candidate dashboardscreen of FIG. 18) including information pertaining to the selectedsequence. The information may pertain to a structure of the sequence, acorrelation heatmap, experimental data, a list of probabilistic scoresgenerated by one or more inference models, external data related to thesequence (e.g., all related external data to a specific peptide, such asdatabase IDs, aliases, synonyms, etc.), or some combination thereof. Insome embodiments, the list of probabilistic scores may be represented asviolin plots detailing a success probability of the sequence in aspecific function (e.g., activity such as anti-viral, anti-microbial,anti-fungal, anti-prionic, etc.) across a set of conditions (e.g., queryparameters).

In some embodiments, the processing device may receive, in the GUI, oneor more parameters pertaining to one or more machine learning models 132of the artificial intelligence engine 140. The one or more parametersmay refer to hyper parameters and may pertain to one or more constraints(e.g., epochs, batch sizes, attention, processor usage, memory usage,execution time, etc.) for the one or more machine learning models toimplement when using the solution space to perform one or more trials.

In some embodiments, the processing device may receive, using agraphical element of the second screen, a selection of a sequence fromthe subset of the set of sequences. The processing device may cause thesequence to be manufactured, synthesized, or produced.

FIG. 22 illustrates example operations of a method 2200 for receivingand presenting of one or more results of performing a selected trialusing a machine learning model according to certain embodiments of thisdisclosure. Method 2200 includes operations performed by processors of acomputing device (e.g., any component of FIG. 1, such as computingdevice 102, server 128 executing the artificial intelligence engine 140,etc.). In some embodiments, one or more operations of the method 2200are implemented in computer instructions stored on a memory device andexecuted by a processing device. The method 2200 may be performed in thesame or a similar manner as described above in regard to method 400. Theoperations of the method 2200 may be performed in some combination withany of the operations of any of the methods described herein.

At block 2202, the processing device may receive a selection of a trialconfigured to be performed by a machine learning model 132. The machinelearning model may use the solution space generated, as described withreference to FIG. 23. The trial may include traversing the solutionspace according to a specific route, a random route, or a combination ofa specific route and a random route. The traversal may result in pointshaving different activities in the solution space. The points mayrepresent a sequence and may be referred to as a candidate drug compoundherein. The traversal may specify a particular location of a point as astarting point or a particular location of a destination point. Thetraversal may or may not specify the route to traverse to get from thestarting point to the destination point. In some embodiments, thetraversal may just specify a starting point or a destination point, andthe machine learning model 132 may randomly traverse the solution spaceto generate different sequences having different activities. Whiletraversing the surface of the solution space, the one or more machinelearning models 132 may be trained to perform maximization functions orminimization functions. For example, the machine learning model maymeasure level of activity at some or all of the points on the surface ofthe solution space and perform a maximization function by traversing thepoints having the maximum level of activity relative to other points inproximity. In some embodiments, the machine learning model may measurelevel of activity at some or all of the points on the surface of thesolution space and perform a minimization function by traversing thepoints having the minimum level of activity relative to other proximatepoints. In some embodiments, the machine learning model may be trainedto perform a combination of minimization and maximization functionswhile performing the traversals.

The selection of the trial may be transmitted to the artificialintelligence engine 140. The artificial intelligence engine 140 may usethe one or more machine learning models 132 to perform the selectedtrial using the solution space. At block 2204, the processing device ofthe computing device 102 may receive, from the artificial intelligenceengine 140, one or more results of performing the trial. The one or moreresults may (i) provide a location of a point reached in the solutionspace after performing a traversal of the solution space defined by thetrial, or (ii) provide a metric of one or more of the machine learningmodels 132 used by the artificial intelligence engine 140 to perform thetrial. The metric may pertain to the process graphic processing unit(GPU) usage (%), the process GPU power usage (%), the process GPU memoryallocated (%), the process GPU time spent accessing memory (%), and theprocess GPU temperature (degrees, e.g., Celsius) (as shown in FIG. 17).The one or more results may be presented on a user interface of thecomputing device 102. The one or more results may be compared to selectthe one or more machine learning models that reached or came closest toa desired point in the solution space, took a desired route (or as closeto the desire route as possible) during traversal to the point,generated a desired sequence having desired activity levels, consumedthe least or a lesser amount of processor resources, generated thelowest or a lower temperature for the graphic processing unit, consumedthe least or a lesser amount of memory resources, or some combinationthereof. The machine learning models not selected may be subsequentlytuned to attempt to improve their results when subsequently performingthe same or different trials.

FIG. 23 illustrates example operations of a method 2300 for using abusiness intelligence screen to select a desired target product profilefor sequences according to certain embodiments of this disclosure.Method 2300 includes operations performed by processors of a computingdevice (e.g., any component of FIG. 1, such as computing device 102,server 128 executing the artificial intelligence engine 140, etc.). Insome embodiments, one or more operations of the method 2300 areimplemented in computer instructions stored on a memory device andexecuted by a processing device. The method 2300 may be performed in thesame or a similar manner as described above in regard to method 400. Theoperations of the method 2300 may be performed in some combination withany of the operations of any of the methods described herein.

At block 2302, the processing device may receive, from a graphicalelement of a business intelligence screen of the graphical userinterface (GUI), a target product profile. The target product profilemay include pharmacology data, pharmacokinetic data, activity data,manufacturing data (e.g., cost to manufacture, requirements formanufacturing, etc.), compliance data, clinical trial data, or somecombination thereof. The target product profile may be transmitted tothe artificial intelligence engine 140. The artificial intelligenceengine 140 may execute one or more machine learning models 132 trainedto generate or search for sequences that match the target productprofile to within a certain threshold level (e.g., percentage, partial,exact, etc.).

At block 2304, the processing device may receive, from the artificialintelligence engine 140, a second subset of the set of sequences. Thesecond subset of the set of sequences may be selected based on thetarget product profile.

At block 2306, the processing device may present, in the GUI, the secondsubset of the set of sequences. The GUI may include one or moregraphical elements that enable the user to drill-down to view detaileddata pertaining to one or more of the sequences matching (partially orexactly) the target product profile. The GUI may include a graphicalelement that enables selecting one or more sequences to manufacture,produce, synthesize, or the like.

FIG. 24 illustrates example computer system 2400 which can perform anyone or more of the methods described herein, in accordance with one ormore aspects of the present disclosure. In one example, computer system2400 may correspond to the computing device 102 (e.g., user computingdevice), one or more servers 128 of the computing system 116, thetraining engine 130, or any suitable component of FIG. 1. The computersystem 2400 may be capable of executing application 118 or the one ormore machine learning models 132 of FIG. 1. The computer system may beconnected (e.g., networked) to other computer systems in a LAN, anintranet, an extranet, or the Internet. The computer system may operatein the capacity of a server in a client-server network environment. Thecomputer system may be a personal computer (PC), a tablet computer, awearable (e.g., wristband), a set-top box (STB), a personal DigitalAssistant (PDA), a mobile phone, a camera, a video camera, or any devicecapable of executing a set of instructions (sequential or otherwise)that specify actions to be taken by that device. Further, while only asingle computer system is illustrated, the term “computer” shall also betaken to include any collection of computers that individually orjointly execute a set (or multiple sets) of instructions to perform anyone or more of the methods discussed herein.

The computer system 2400 includes a processing device 2402, a volatilememory 2404 (e.g., random access memory (RAM)) and a non-volatile memory2406 (e.g., read-only memory (ROM), flash memory, solid state drives(SSDs), and a data storage device 1108, which communicate with eachother via a bus 2410.

Processing device 2402 represents one or more general-purpose processingdevices such as a microprocessor, central processing unit, or the like.More particularly, the processing device 2402 may be a complexinstruction set computing (CISC) microprocessor, reduced instruction setcomputing (RISC) microprocessor, very long instruction word (VLIW)microprocessor, or a processor implementing other instruction sets orprocessors implementing a combination of instruction sets. Theprocessing device 2402 may also be one or more special-purposeprocessing devices such as an application specific integrated circuit(ASIC), a system on a chip, a field programmable gate array (FPGA), adigital signal processor (DSP), network processor, or the like. Theprocessing device 2402 may include more than one processing device, andeach of the processing devices may be the same or different types. Theprocessing device 2402 may include or be communicatively coupled to oneor more accelerators 2403 configured to offload various data-processingtasks from the processing device 2402. The processing device 2402 isconfigured to execute instructions for performing any of the operationsand steps discussed herein.

The computer system 2400 may further include a network interface device2412. The network interface device 2412 may be configured to communicatedata via any suitable communication protocol. In some embodiments, thenetwork interface devices 2412 may enable wireless (e.g., WiFi,Bluetooth, ZigBee, etc.) or wired (e.g., Ethernet, etc.) communications.The computer system 2400 also may include a video display 2414 (e.g., aliquid crystal display (LCD), a light-emitting diode (LED), an organiclight-emitting diode (OLED), a quantum LED, a cathode ray tube (CRT), ashadow mask CRT, an aperture grille CRT, or a monochrome CRT), one ormore input devices 2416 (e.g., a keyboard or a mouse), and one or morespeakers 2418 (e.g., a speaker). In one illustrative example, the videodisplay 2414 and the input device(s) 2416 may be combined into a singlecomponent or device (e.g., an LCD touch screen).

The data storage device 2416 may include a computer-readable medium 2420on which the instructions 2422 embodying any one or more of the methods,operations, or functions described herein is stored. The instructions2422 may also reside, completely or at least partially, within the mainmemory 2404 or within the processing device 2402 during executionthereof by the computer system 2400. As such, the main memory 2404 andthe processing device 2402 also constitute computer-readable media. Theinstructions 2422 may further be transmitted or received over a networkvia the network interface device 2412.

While the computer-readable storage medium 2420 is shown in theillustrative examples to be a single medium, the term “computer-readablestorage medium” should be taken to include a single medium or multiplemedia (e.g., a centralized or distributed database, or associated cachesand servers) that store the one or more sets of instructions. The term“computer-readable storage medium” shall also be taken to include anymedium capable of storing, encoding, or carrying a set of instructionsfor execution by the machine, where such set of instructions cause themachine to perform any one or more of the methodologies of the presentdisclosure. The term “computer-readable storage medium” shallaccordingly be taken to include, but not be limited to, solid-statememories, optical media, and magnetic media.

None of the description in this application should be read as implyingthat any particular element, step, or function is an essential elementthat must be included in the claim scope. The scope of patented subjectmatter is defined only by the claims. Moreover, none of the claims isintended to invoke 35 U.S.C. § 112(f) unless the exact words “means for”are followed by a participle.

Consistent with the above disclosure, the examples of systems and methodenumerated in the following clauses are specifically contemplated andare intended as a non-limiting set of examples.

Clause 1. A method comprising:

generating a design space for a peptide for an application, wherein thegenerating comprises:

identifying a plurality of sequences for the peptide; and

updating the plurality of sequences by determining, for each of theplurality of sequences, a respective plurality of activities pertainingto the application, wherein the updating produces an updated pluralityof sequences each having an updated respective plurality of activities;

generating, based on the updated plurality of sequences each having theupdated respective plurality of activities, a solution space within thedesign space, wherein the solution space comprises a target subset ofthe updated plurality of sequences each having the updated respectiveplurality of activities;

performing, using a machine learning model to process the solutionspace, one or more trials to identify a candidate drug compound thatrepresents a sequence having at least one level of activity that exceedsone or more threshold levels; and

transmitting information describing the candidate drug compound to acomputing device.

Clause 2. The method of any preceding clause, wherein the generating thesolution space within the design space is performed by a second machinelearning model trained to measure, based on a query parameter, a levelof the updated respective plurality of activities, wherein the queryparameter comprises a sequence parameter.

Clause 3. The method of any preceding clause, further comprising:

receiving the query parameter; and

generating, based on the query parameter and the updated plurality ofsequences each having the updated respective plurality of activities,the solution space within the design space, wherein the solution spacecomprises the target subset of the plurality of sets of the updatedplurality of sequences, and each sequence of the updated plurality ofsequences in the target subset comprises the updated respectiveplurality of activities that are modified in view of the queryparameter.

Clause 4. The method of any preceding clause, wherein the generating thesolution space within the design space further comprises performing,using the query parameter and the updated plurality of sequences eachhaving the updated respective plurality of activities, uniform manifoldapproximation and projection (UMAP) for dimension reduction to identifythe target subset.

Clause 5. The method of any preceding clause, wherein the receiving thequery parameter further comprises receiving the query parameter from agraphical element of a user interface presenting the design space.

Clause 6. The method of any preceding clause, further comprising:

receiving the query parameter and a desired threshold level of a targetactivity for the query parameter that the target subset is to exceed inorder to be included in the solution space.

Clause 7. The method of any preceding clause, wherein the applicationcomprises at least one of:

anti-infective,

anti-cancer,

antimicrobial,

anti-viral,

anti-fungal,

anti-inflammatory,

anti-cholinergic,

anti-dopaminergic,

anti-serotonergic,

anti-noradrenergic,

anti-prionic,

functional biomaterials comprising adhesives, sealants, binders,chelates, diagnostic reporters, or some combination thereof, and

structural biomaterials comprising biopolymers, encapsulation films,flocculants, desiccants, or some combination thereof.

Clause 8. The method of any preceding clause, further comprising:

receiving a selection of a sequence from the target subset; and

providing information pertaining to the sequence, wherein theinformation comprises at least classes of:

proteins,

protein-to-protein interactions,

protein-ligand interactions,

protein homology and phylogeny,

sequence and structure motifs,

chemical and physical stability,

pharmacological associations,

systems biology,

protein folding, or

some combination thereof.

Clause 9. The method of any preceding clause, further comprising:

providing the solution space to the computing device for presentation asa topographical map in a user interface of the computing device, whereinthe topographical map comprises a plurality of indications that eachrepresent a level of activity for a sequence at a given point on thetopographical map.

Clause 10. The method of any preceding clause, further comprisingcausing the candidate drug compound to be manufactured.

Clause 11. The method of any preceding clause, wherein the updatedrespective plurality of activities comprises immunomodulatory activity,receptor binding activity, self-aggregation, cell-penetrating activity,anti-viral activity, peptidergic activity, or some combination thereof.

Clause 12. The method of any preceding clause, further comprising:

determining one or more metrics of the machine learning model thatperforms the one or more trials, wherein the one or more metricscomprise memory usage, graphic processing unit temperature, power usage,processor usage, central processing unit temperature, or somecombination thereof; and

comparing the one or more metrics to one or more second metrics of asecond machine learning model that performs the one or more trials.

Clause 13. A tangible, non-transitory computer-readable medium storinginstructions that, when executed, cause a processing device to:

generate a design space for a peptide for an application, wherein thegenerating comprises:

identifying a plurality of sequences for the peptide; and

updating the plurality of sequences by determining, for each of theplurality of sequences, a respective plurality of activities pertainingto the application, wherein the updating produces an updated pluralityof sequences each having an updated respective plurality of activities;

generate, based on the updated plurality of sequences each having theupdated respective plurality of activities, a solution space within thedesign space, wherein the solution space comprises a target subset ofthe updated plurality of sequences each having the updated respectiveplurality of activities;

perform, using a machine learning model to process the solution space,one or more trials to identify a candidate drug compound that representsa sequence having at least one level of activity that exceeds one ormore threshold levels; and

transmit information describing the candidate drug compound to acomputing device.

Clause 14. The computer-readable medium of any preceding clause, whereinthe generating the solution space within the design space is performedby a second machine learning model trained to measure, based on a queryparameter, a level of the updated respective plurality of activities,wherein the query parameter comprises a sequence parameter.

Clause 15. The computer-readable medium of any preceding clause, whereinthe processing device is further to:

receive the query parameter; and

generate, based on the query parameter and the updated plurality ofsequences each having the updated respective plurality of activities,the solution space within the design space, wherein the solution spacecomprises the target subset of the plurality of sets of the updatedplurality of sequences, and each sequence of the updated plurality ofsequences in the target subset comprises the updated respectiveplurality of activities that are modified in view of the queryparameter.

Clause 16. The computer-readable medium of any preceding clause, whereinthe generating the solution space within the design space furthercomprises performing, using the query parameter and the updatedplurality of sequences each having the updated respective plurality ofactivities, uniform manifold approximation and projection (UMAP) fordimension reduction to identify the target subset.

Clause 17. The computer-readable medium of any preceding clause, whereinthe receiving the query parameter further comprises receiving the queryparameter from a graphical element of a user interface presenting thedesign space.

Clause 18. The computer-readable medium of any preceding clause, whereinthe processing device is further to:

receive the query parameter and a desired threshold level of a targetactivity for the query parameter that the target subset is to exceed inorder to be included in the solution space.

Clause 19. A system comprising:

a memory device storing instructions; and

a processing device communicatively coupled to the memory device, theprocessing device executes the instructions to:

generate a design space for a peptide for an application, wherein thegenerating comprises:

identifying a plurality of sequences for the peptide; and

updating the plurality of sequences by determining, for each of theplurality of sequences, a respective plurality of activities pertainingto the application, wherein the updating produces an updated pluralityof sequences each having an updated respective plurality of activities;

generate, based on the updated plurality of sequences each having theupdated respective plurality of activities, a solution space within thedesign space, wherein the solution space comprises a target subset ofthe updated plurality of sequences each having the updated respectiveplurality of activities;

perform, using a machine learning model to process the solution space,one or more trials to identify a candidate drug compound that representsa sequence having at least one level of activity that exceeds one ormore threshold levels; and

transmit information describing the candidate drug compound to acomputing device.

Clause 20. The system of any preceding clause, wherein the generatingthe solution space within the design space is performed by a secondmachine learning model trained to measure, based on a query parameter, alevel of the updated respective plurality of activities, wherein thequery parameter comprises a sequence parameter.

Clause 21. A method for presenting, on a computing device, a graphicaluser interface (GUI) of a therapeutic tool, the method comprising:

presenting, in a first screen of the GUI, a design space for a proteinfor an application, wherein the design space comprises a plurality ofsequences each containing a respective plurality of activitiespertaining to the application;

receiving, via a graphical element in the first screen, a selection ofone or more query parameters of the design space; and

presenting, in a second screen of the GUI, a solution space thatincludes a subset of the plurality of sequences each containing therespective plurality of activities, wherein the subset of the pluralityof sequences is selected based on the one or more query parameters.

Clause 22. The method of any preceding clause, wherein the second screencomprises:

a first portion presenting one or more color-coded clusters representingthe subset of the plurality of sequences, and

a second portion presenting data pertaining to the subset of theplurality of sequences represented by the one or more color-codedclusters, wherein the data describes one or more objects associated withthe subset of the plurality of sequences, and the one or more objectscomprise a candidate drug compound, an activity, an interaction, a drug,a gene, a pathway , a physical descriptor, a characteristic, aninteraction, a folding property, a wave property, a stability ofmodification, or some combination thereof.

Clause 23. The method of any preceding clause, wherein the one or morecolor-coded clusters represent, using an energy correlation , eachsequence in the subset, and the energy correlation comprises acorrelation between each position of each sequence in the subset andother positions of other sequences in the subset.

Clause 24. The method of any preceding clause, wherein the solutionspace is presented as a topographical map in the GUI, wherein thetopographical map comprises a plurality of indications that eachrepresent a level of activity for a sequence associated with a givenpoint on the topographical map.

Clause 25. The method of any preceding clause, wherein the design spaceis generated based on a knowledge graph pertaining to peptides and thedesign space is presented as a two-dimensional (2D) elevation map, athree-dimensional (3D) shape or an n-dimensional (nD) mathematicalrepresentation.

Clause 26. The method of any preceding clause, wherein the solutionspace is generated within the design space by one or more machinelearning models trained to measure, based on the query parameter, arespective level of one or more of the respective plurality ofactivities of each of the plurality of sequences in the subset, whereinthe query parameter comprises a sequence parameter.

Clause 27. The method of any preceding clause, further comprising:

receiving, using a graphical element of the second screen, a selectionof a sequence from the subset of the plurality of sequences, wherein theselection is based on the sequence being previously untraversed; and

responsive to the selection of the sequence, presenting, in the secondscreen, additional information pertaining to the sequence, wherein theadditional information comprises a candidate drug compound, aninteraction, an activity, a drug, a gene, a pathway, or some combinationthereof.

Clause 28. The method of any preceding clause, further comprising:

receiving, using a graphical element of the second screen, a selectionof a sequence from the subset of the plurality of sequences; and

presenting, in a third screen of the GUI, a candidate dashboardcomprising information pertaining to the sequence, wherein theinformation pertains to a structure of the sequence, a correlationheatmap, experimental data, a list of probabilistic scores generated byinference models, external data related to the sequence, or somecombination thereof.

Clause 29. The method of any preceding clause, further comprising:

receiving a selection of a trial configured to be performed by a machinelearning model, wherein the machine learning model uses the solutionspace; and

receiving, from an artificial intelligence engine, one or more resultsof performing the trial, wherein the one or more results:

provide a location of a point reached in the solution space afterperforming a traversal of the solution space defined by the trial, and

provide a metric of a machine learning model used by the artificialintelligence engine to perform the trial, wherein the metric pertains tomemory usage, graphic processing unit temperature, power usage,processor usage, central processing unit temperature, or somecombination thereof.

Clause 30. The method of any preceding clause, further comprising:

receiving, from a graphical element of a business intelligence screen ofthe GUI, a target product profile, wherein the target product profilecomprises pharmacology data, pharmacokinetic data, pharmacodynamic data,activity data, manufacturing data, compliance data, clinical trial data,or some combination thereof;

receiving, from an artificial intelligence engine, a second subset ofthe plurality of sequences, wherein the second subset of the pluralityof sequences is selected based on the target product profile; and

presenting, in the GUI, the second subset of the plurality of sequences.

Clause 31. The method of any preceding clause, further comprising:

receiving, in the GUI, one or more parameters pertaining to one or moremachine learning models of an artificial intelligence engine, whereinthe one or more parameters pertain to one or more constraints for theone or more machine learning models to implement when performing one ormore trials using the solution space.

Clause 32. The method of any preceding clause, wherein the therapeutictool is a peptide therapeutic tool.

Clause 33. The method of any preceding clause, wherein the protein is apeptide.

Clause 34. The method of any preceding clause, wherein the one or morequery parameters comprise a plurality of biomedical ontology terms, aplurality of non-biomedical ontology terms, or some combination thereof.

Clause 35. The method of any preceding clause, wherein the plurality ofbiomedical ontology terms pertain to indications, genes, symptoms, orsome combination thereof, and the plurality of non-biomedical ontologyterms pertain to characteristics, descriptors, or some combinationthereof.

Clause 36. The method of any preceding clause, further comprising:

receiving, using a graphical element of the second screen, a selectionof a sequence from the subset of the plurality of sequences; and

causing the sequence to be manufactured, synthesized, or produced.

Clause 37. A tangible, non-transitory computer-readable medium storinginstructions that, when executed, cause a processing device to:

presenting, in a first screen of a graphical user interface (GUI), adesign space for a protein for an application, wherein the design spacecomprises a plurality of sequences each containing a respectiveplurality of activities pertaining to the application;

receiving, via a graphical element in the first screen, a selection ofone or more query parameters of the design space; and

presenting, in a second screen of the GUI, a solution space thatincludes a subset of the plurality of sequences each containing therespective plurality of activities, wherein the subset of the pluralityof sequences is selected based on the one or more query parameters.

Clause 38. The computer-readable medium of any preceding clause, whereinthe second screen comprises:

a first portion presenting one or more color-coded clusters representingthe subset of the plurality of sequences, and

a second portion presenting data pertaining to the subset of theplurality of sequences represented by the one or more color-codedclusters, wherein the data describes one or more objects associated withthe subset of the plurality of sequences, and the one or more objectscomprise a candidate drug compound, an activity, an interaction, a drug,a gene, a pathway, a physical descriptor, a characteristic, aninteraction, a folding property, a wave property, a stability ofmodification, or some combination thereof.

Clause 39. The computer-readable medium of any preceding clause, whereinthe one or more color-coded clusters represent, using an energycorrelation, each sequence in the subset, and the energy correlationcomprises a correlation between each position of each sequence in thesubset and other positions of other sequences in the subset.

Clause 40. A system comprising:

a memory device storing instructions; and

a processing device communicatively coupled to the memory device, theprocessing device executes the instructions :

present, in a first screen of a graphical user interface (GUI), a designspace for a protein for an application, wherein the design spacecomprises a plurality of sequences each containing a respectiveplurality of activities pertaining to the application;

receive, via a graphical element in the first screen, a selection of oneor more query parameters of the design space; and

present, in a second screen of the GUI, a solution space that includes asubset of the plurality of sequences each containing the respectiveplurality of activities, wherein the subset of the plurality ofsequences is selected based on the one or more query parameters.

What is claimed is:
 1. A method comprising: generating a design spacefor a peptide for an application, wherein the generating comprises:identifying a plurality of sequences for the peptide; and updating theplurality of sequences by determining, for each of the plurality ofsequences, a respective plurality of activities pertaining to theapplication, wherein the updating produces an updated plurality ofsequences each having an updated respective plurality of activities;generating, based on the updated plurality of sequences each having theupdated respective plurality of activities, a solution space within thedesign space, wherein the solution space comprises a target subset ofthe updated plurality of sequences each having the updated respectiveplurality of activities; performing, using a machine learning model toprocess the solution space, one or more trials to identify a candidatedrug compound that represents a sequence having at least one level ofactivity that exceeds one or more threshold levels; and transmittinginformation describing the candidate drug compound to a computingdevice.
 2. The method of claim 1, wherein the generating the solutionspace within the design space is performed by a second machine learningmodel trained to measure, based on a query parameter, a level of theupdated respective plurality of activities, wherein the query parametercomprises a sequence parameter.
 3. The method of claim 2, furthercomprising: receiving the query parameter; and generating, based on thequery parameter and the updated plurality of sequences each having theupdated respective plurality of activities, the solution space withinthe design space, wherein the solution space comprises the target subsetof the plurality of sets of the updated plurality of sequences, and eachsequence of the updated plurality of sequences in the target subsetcomprises the updated respective plurality of activities that aremodified in view of the query parameter.
 4. The method of claim 3,wherein the generating the solution space within the design spacefurther comprises performing, using the query parameter and the updatedplurality of sequences each having the updated respective plurality ofactivities: uniform manifold approximation and projection (UMAP) fordimension reduction to identify the target subset, linear decomposition,principal component analysis (PCA), kernel PCA, matrix factorization,generalized discriminant analysis, linear discriminant analysis,autoencoding, or some combination thereof.
 5. The method of claim 3,wherein the receiving the query parameter further comprises receivingthe query parameter from a graphical element of a user interfacepresenting the design space.
 6. The method of claim 3, furthercomprising: receiving the query parameter and a desired threshold levelof a target activity for the query parameter that the target subset isto exceed in order to be included in the solution space.
 7. The methodof claim 1, wherein the application comprises at least one of:anti-infective, anti-cancer, antimicrobial, anti-viral, anti-fungal,anti-inflammatory, anti-cholinergic, anti-dopaminergic,anti-serotonergic, anti-noradrenergic, immunomodulatory,neuromodulatory, a physiological effect caused by a signaling peptide,anti-prionic, functional biomaterials comprising adhesives, sealants,binders, chelates, diagnostic reporters, or some combination thereof,and structural biomaterials comprising biopolymers, encapsulation films,flocculants, desiccants, or some combination thereof.
 8. The method ofclaim 1, further comprising: receiving a selection of a sequence fromthe target subset; and providing information pertaining to the sequence,wherein the information comprises at least classes of: proteincharacteristics, protein-to-protein interactions, protein-ligandinteractions, protein homology and phylogeny, sequence and structuremotifs, chemical and physical stability, attributes expressed insolubility data, related structures, related drugs, chemical synthesis,biological synthesis, intellectual property data, clinical data, marketdata, pharmacological associations, systems biology, protein folding, orsome combination thereof.
 9. The method of claim 1, further comprising:providing the solution space to the computing device for presentation asa topographical map in a user interface of the computing device, whereinthe topographical map comprises a plurality of indications that eachrepresent a level of activity for a sequence at a given point on thetopographical map.
 10. The method of claim 1, further comprising causingthe candidate drug compound to be manufactured.
 11. The method of claim1, wherein the updated respective plurality of activities comprisesimmunomodulatory activity, receptor binding activity, self-aggregation,cell-penetrating activity, anti-viral activity, peptidergic activity, orsome combination thereof.
 12. The method of claim 1, further comprising:determining one or more metrics of the machine learning model thatperforms the one or more trials, wherein the one or more metricscomprise memory usage, graphic processing unit temperature, power usage,processor usage, central processing unit temperature, or somecombination thereof; and comparing the one or more metrics to one ormore second metrics of a second machine learning model that performs theone or more trials.
 13. A tangible, non-transitory computer-readablemedium storing instructions that, when executed, cause a processingdevice to: generate a design space for a peptide for an application,wherein the generating comprises: identifying a plurality of sequencesfor the peptide; and updating the plurality of sequences by determining,for each of the plurality of sequences, a respective plurality ofactivities pertaining to the application, wherein the updating producesan updated plurality of sequences each having an updated respectiveplurality of activities; generate, based on the updated plurality ofsequences each having the updated respective plurality of activities, asolution space within the design space, wherein the solution spacecomprises a target subset of the updated plurality of sequences eachhaving the updated respective plurality of activities; perform, using amachine learning model to process the solution space, one or more trialsto identify a candidate drug compound that represents a sequence havingat least one level of activity that exceeds one or more thresholdlevels; and transmit information describing the candidate drug compoundto a computing device.
 14. The computer-readable medium of claim 13,wherein the generating the solution space within the design space isperformed by a second machine learning model trained to measure, basedon a query parameter, a level of the updated respective plurality ofactivities, wherein the query parameter comprises a sequence parameter.15. The computer-readable medium of claim 14, wherein the processingdevice is further to: receive the query parameter; and generate, basedon the query parameter and the updated plurality of sequences eachhaving the updated respective plurality of activities, the solutionspace within the design space, wherein the solution space comprises thetarget subset of the plurality of sets of the updated plurality ofsequences, and each sequence of the updated plurality of sequences inthe target subset comprises the updated respective plurality ofactivities that are modified in view of the query parameter.
 16. Thecomputer-readable medium of claim 15, wherein the generating thesolution space within the design space further comprises performing,using the query parameter and the updated plurality of sequences eachhaving the updated respective plurality of activities, uniform manifoldapproximation and projection (UMAP) for dimension reduction to identifythe target subset, linear decomposition, pca, kernel pca, matrixfactorization, generalized discriminant analysis, linear discriminantanalysis, autoencoding, or some combination thereof.
 17. Thecomputer-readable medium of claim 15, wherein the receiving the queryparameter further comprises receiving the query parameter from agraphical element of a user interface presenting the design space. 18.The computer-readable medium of claim 15, wherein the processing deviceis further to: receive the query parameter and a desired threshold levelof a target activity for the query parameter that the target subset isto exceed in order to be included in the solution space.
 19. A systemcomprising: a memory device storing instructions; and a processingdevice communicatively coupled to the memory device, the processingdevice executes the instructions to: generate a design space for apeptide for an application, wherein the generating comprises:identifying a plurality of sequences for the peptide; and updating theplurality of sequences by determining, for each of the plurality ofsequences, a respective plurality of activities pertaining to theapplication, wherein the updating produces an updated plurality ofsequences each having an updated respective plurality of activities;generate, based on the updated plurality of sequences each having theupdated respective plurality of activities, a solution space within thedesign space, wherein the solution space comprises a target subset ofthe updated plurality of sequences each having the updated respectiveplurality of activities; perform, using a machine learning model toprocess the solution space, one or more trials to identify a candidatedrug compound that represents a sequence having at least one level ofactivity that exceeds one or more threshold levels; and transmitinformation describing the candidate drug compound to a computingdevice.
 20. The system of claim 19, wherein the generating the solutionspace within the design space is performed by a second machine learningmodel trained to measure, based on a query parameter, a level of theupdated respective plurality of activities, wherein the query parametercomprises a sequence parameter.